What We Treat:

Below is a list of conditions for which mesenchymal stem cells have shown excellent safety and efficacy, to varying degrees, in clinical trials in humans, and/or pre-clinical studies in animals. Each diagnosis is followed by a list of some of the most important studies published in high quality peer reviewed medical journals describing results of MSC treatment. This list if not exhaustive and treatment is available for other less common conditions.

Following each study is a short synopsis, including a non-technical summary, of the main point(s) of the study. At the end of the article list is a link to our study on clinicaltrials.gov if one exists for that condition.

Some of the studies listed may use fetal or embryonic cells and we include them because efficacy may be similar with the adult mesenchymal umbilical cells we use, but we wish to emphasize that we do not use fetal or embryonic cells for any of our patients.

Please contact us with any questions regarding these or other conditions at care@thepsci.com or 847-699-6810 x207.

• Ankylosing Spondylitis
• Anti-Aging
• Autism
• Bell's Palsy/ Trigeminal Neuralgia
• Cerebral Palsy
• Chronic Obstructive Pulmonary Disease
• Diabetes: types 1 and 2
• Erectile dysfunction
• Hearing Loss
• Peyronie’s Disease
• Eye disease
• Fractures
• Heart Failure
• Inflammatory Bowel Disease
• Interstitial Cystitis
• Kidney Disease
• Leg and foot ulcers
• Lupus
• Multiple Sclerosis
• Multiple System Atrophy
• Osteoarthritis
• Parkinson’s Disease
• Rheumatoid arthritis
• Sarcoidosis
• Scleroderma
• Sjogren's Syndrome
• spinal cord injury with paralysis
• Traumatic Brain Injury

Ankylosing spondylitis

• Wang P, Li Y, Huang L, Yang J, Yang R, Deng W, Liang B, Dai L, Meng Q, Gao L, Chen X, Shen J, Tang Y, Zhang X, Hou J, Ye J, Chen K, Cai Z, Wu Y, Shen H. Effects and safety of allogenic mesenchymal stem cell intravenous infusion in active ankylosing spondylitis patients who failed NSAIDs: a 20-week clinical trial. Cell Transplant. 2014;23(10):1293-303. doi: 10.3727/096368913X667727. Epub 2013 May 22. PMID: 23711393.
  31 patients were treated with cultured allogeneic bone marrow derived mesenchymal stem cells administered intravenously. ASAS20 responders were determined to be 77.4% at 4 weeks. Mean ASAS20 response duration was 7.1 weeks. Average total inflammation extent, as determined by MRI was significantly reduced at the 20^th week when compared to baseline.  Intravenous cultured allogeneic bone marrow mesenchymal cells showed improvement in symptoms, but the average length of improvement in symptoms was for only 7 weeks. Total inflammation was significantly reduced up until 20 weeks.
• Li A, Tao Y, Kong D, Zhang N, Wang Y, Wang Z, Wang Y, Wang J, Xiao J, Jiang Y, Liu X, Zheng C. Infusion of umbilical cord mesenchymal stem cells alleviates symptoms of ankylosing spondylitis. Exp Ther Med. 2017 Aug;14(2):1538-1546. doi: 10.3892/etm.2017.4687. Epub 2017 Jun 27. PMID: 28781629; PMCID: PMC5526206.
  5 patients treated with allogeneic cultured umbilical cord mesenchymal stem cells administered intravenously. Inflammatory markers including ESR and CRP had a downward trend in all 5 patients at 6 months. BASDAI demonstrated significant reduction at 3 and 6 month reevaluations. Another index, the BASMI worsened after 6 month follow up.  A third index, the BSAFI, showed an improvement trend. Intravenous infusion of cultured allogeneic umbilical mesenchymal stem cells demonstrated improvement at 6 months in inflammatory markers. When assessing disease activity, there were mixed results across three different metrics.

Anti-Aging

• Golpanian S, DiFede DL, Khan A, et al. Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. J Gerontol A Biol Sci Med Sci. 2017;72(11):1505-1512. doi:10.1093/gerona/glx056
  15 patients recruited and split into 3 groups. Group 1 received 20 million allogeneic bone marrow derived mesenchymal stem cells, group 2 received 100 million allogeneic bone marrow derived mesenchymal stem cells and group 3 received 200 million allogeneic bone marrow derived mesenchymal stem cells. All treatments administered intravenously. Groups 1 and 2 showed significant improvement at 6MWT at 6 months. Group 2 also showed significant improvement of physical components SF-36 at 6 months. TNF-alpha showed significant reduction in groups 2 and 3 at 6 months. Intravenous administration of allogeneic bone marrow MSCs demonstrated efficacy in improvements in 6MWT, SF-36 and serum TNF-alpha at 6 months. The 100 million cell dose demonstrated the most efficacy.
• Tompkins BA, DiFede DL, Khan A, Landin AM, Schulman IH, Pujol MV, Heldman AW, Miki R, Goldschmidt-Clermont PJ, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Da Fonseca M, Golpanian S, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Green G, Oliva AA, Hare JM. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1513-1522. doi: 10.1093/gerona/glx137. PMID: 28977399; PMCID: PMC5861900.
  30 patients enrolled. 10 patients treated with placebo, 10 patients treated with 100 million allogeneic mesenchymal stem cells and 10 patients treated with 200 million allogeneic mesenchymal stem cells. All treatments administered intravenously. Physical parameters including 6MWT, SPPB and FEV1 all showed improvement at 6 months in the 100 million dose group. At 6 months, immune biomarkers including early activation of CD69, CD8% and CD4/CD8 ratio showed improvement in the 200 million cell group. Late activation of CD25 showed improvement in both the 100 million and 200 million cell groups. TNF-alpha levels showed improvement only in the 100 million cell group. The 100million group demonstrated improvement in the sexual quality of life questionnaire but only for females.
  Intravenous infusion of allogeneic MSCs showed improvement in physical and immune biomarkers. The group receiving 100 million stem cells demonstrated more improvement in physical parameters at 6 months while the 200 million group demonstrated superior efficacy in reducing immune biomarkers associated with aging.

Click here for the clinical trial for Anti-Aging

Autism

For reference:

CARS/ABC: no autism <30, mild/moderate = 30-36.5, severe >36.5

CGI-SI: 1=normal, 7=severe

ATEC: 0-180, 180=severe

• Lv YT, Zhang Y, Liu M, Qiuwaxi JN, Ashwood P, Cho SC, Huan Y, Ge RC, Chen XW, Wang ZJ, Kim BJ, Hu X. Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. J Transl Med. 2013 Aug 27;11:196. doi: 10.1186/1479-5876-11-196. PMID: 23978163; PMCID: PMC3765833.
  Dr. Lv’s clinical trial in China followed 37 patients. 14 were treated with cord blood mononuclear cells in one dose of 2x10^6 cells per kilogram given by IV, then 3 doses of 2x10^6 mononuclear cells per kilogram given intrathecally. Another 9 patients were treated with 2 infusions of 2x10^6 cord blood mononuclear cells per kilogram by IV, 2 intrathecal injections of 2x10^6 cord blood mononuclear cells per kg, and 2 doses of 1x10^6 umbilical cord mesenchymal stem cells per kg intrathecally. Another 14 patients served as a control group. By the end of 24 weeks of follow up, the combined cord blood and umbilical group showed a CARS improvement of 9 points compared to the cord blood only group and the control, which showed no change. According to the CGI scores, 9/14 of the cord blood only patients improved while the other 5 showed no change. All 9 patients of the combined group improved, and the control group had 12 improve and 1 with no change.
  Intrathecal umbilical cord injection in conjunction with cord blood mononuclear cells had significant improvement at 6 months post treatment. The combination was more effective in reducing symptoms of Autism than cord blood mononuclear cells alone.
• Bradstreet JJ, Sych N, Antonucci N, Klunnik M, Ivankova O, Matyashchuk I, Demchuk M, Siniscalco D. Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-labeled pilot study. Cell Transplant. 2014;23 Suppl 1:S105-12. doi: 10.3727/096368914X684916. Epub 2014 Oct 9. PMID: 25302490.
  Dr. Bradstreet’s USA clinical trial treated 45 patients of mean age 7 with cultured fetal stem cells at a dose of about 50x10^6 HSCs by IV and 15x10^6 neuroprogenitor cells into subcutaneous adipose. After 12 months follow up, the average ATEC score significantly improved from 83 to 59 and the average ABC score significantly improved from 80 to 54.
  Cultured fetal stem cells administered intravenously along with neuroprogenitor cells injected subcutaneously significantly improved the symptoms of Autism 12 months post treatment.
• Dawson G, Sun JM, Davlantis KS, Murias M, Franz L, Troy J, Simmons R, Sabatos-DeVito M, Durham R, Kurtzberg J. Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial. Stem Cells Transl Med. 2017 May;6(5):1332-1339. doi: 10.1002/sctm.16-0474. Epub 2017 Apr 5. PMID: 28378499; PMCID: PMC5442708.
  Dr. Dawson’s clinical trial followed 25 children from age 2 to 6 with banked autologous umbilical cord blood. They were treated with an IV infusion of cord blood with a total nucleated cell count from 1-5x10^7 per kg. The CGI-SI scores show a 22.7% decrease in the number of patients classified as moderately severe or severe. The PDDBI Autism Composite T Score declined by 7.52 over the first 6 months, then by 0.72 from 6 to 12 months, suggesting an improvement in symptoms.
  Autologous umbilical cord blood administered intravenously demonstrated the ability to decrease disease severity and improve symptoms associated with Autism at 12 months. 
• Sharma A, Gokulchandran N, Sane H, Nagrajan A, Paranjape A, Kulkarni P, Shetty A, Mishra P, Kali M, Biju H, Badhe P. Autologous bone marrow mononuclear cell therapy for autism: an open label proof of concept study. Stem Cells Int. 2013;2013:623875. doi: 10.1155/2013/623875. Epub 2013 Aug 25. PMID: 24062774; PMCID: PMC3767048.
  Dr. Sharma’s clinical trial treated 32 patients with autism and followed them for up to 27 months. They were treated with autologous bone marrow mononuclear cells at a dose of 8.2x10^7 cells given intrathecally. 91% of patients showed improved ISAA scores, improving on average from 115.5 to 97. Additionally, 62% were classified as milder on the CGI-I scale, improving on average from 4.5 to 3.
  Autologous bone marrow mononuclear cells from aspirate showed efficacy in decreasing disease severity and improving symptomatology.
• Nguyen Thanh L, Nguyen HP, Ngo MD, Bui VA, Dam PTM, Bui HTP, Ngo DV, Tran KT, Dang TTT, Duong BD, Nguyen PAT, Forsyth N, Heke M. Outcomes of bone marrow mononuclear cell transplantation combined with interventional education for autism spectrum disorder. Stem Cells Transl Med. 2021 Jan;10(1):14-26. doi: 10.1002/sctm.20-0102. Epub 2020 Sep 9. PMID: 32902182; PMCID: PMC7780798.
  Dr. Nguyen Thanh’s clinical trial treated 30 children with autologous bone marrow mononuclear cells infused intrathecally at a dose of 42.3x10^6 cells per kilogram with 2.6x10^6 CD34+ cells. 6 months later, they received a second dose of 40.9x10^6 mononuclear cells per kilogram and 2.1x10^6 CD34+ cells. After 18 months, the average CARS score improved from 50 to 46.5. According to the DSM-5, the number of patients at level 3 of severity decreased from 28 to 18. Overall, 5 children improved all the way to level 1.
  Repeat intrathecal injection of autologous bone marrow mononuclear cells from aspirate demonstrated efficacy in decreasing disease severity at 18 months.
• Riordan NH, Hincapié ML, Morales I, Fernández G, Allen N, Leu C, Madrigal M, Paz Rodríguez J, Novarro N. Allogeneic Human Umbilical Cord Mesenchymal Stem Cells for the Treatment of Autism Spectrum Disorder in Children: Safety Profile and Effect on Cytokine Levels. Stem Cells Transl Med. 2019 Oct;8(10):1008-1016. doi: 10.1002/sctm.19-0010. Epub 2019 Jun 11. PMID: 31187597; PMCID: PMC6766688.
  In Dr. Riordan’s study, 20 patients diagnosed with autism received 36 million umbilical cord mesenchymal stem cells intravenously every 3 months for a total of 9 months. Average pretreatment CARS score was 37.48, which improved to 30.65 on reevaluation at 12 months. The pretreatment average ATEC score was 61.1, which improved to 36.81 at 12 month follow up. Additionally, MDC and TARC are serum markers that when elevated, have shown correlation with autism. The initial pretreatment MDC and TARC levels were 949.6 and 212.35, respectively. At 12 month follow up, both of these values improved to 484.08 and 130.4, respectively.
  Repeated intravenous infusions of umbilical cord mesenchymal stem cells significantly improved CARS and ATEC rating scores and also substantially decreased serum markers indicative of autism disease activity at 12 months.

Click here for the clinical trial for Autism

Bell's Palsy/ Trigeminal Neuralgia

• A preliminary report on stem cell therapy for neuropathic pain in humans
  Dr. Vickers enrolled 10 patients diagnosed with trigeminal neuralgia. Each patient had roughly 100-200g of tissue harvested by tumescent liposuction. The tissue was subsequently digested by colleganse and each patient received an average of 77 million total cells. The SVF was injected into the center or origin of pain, along with the adjacent pain field of the affected branches of the trigeminal nerve.  On a scale from 1-10, the average pain score before treatment was 7.5. 6 months after treatment the pain scores significantly improved to an average of 4.3. 5/9 reported decreased reliance on Gabapentin medication.   SVF with an average of 77 million total cells injected directly into the area of pain demonstrated the ability to significantly decrease pain scores and reduce reliance on neuropathic medication.
• Seffer I, Nemeth Z. Recovery from Bell Palsy after Transplantation of Peripheral Blood Mononuclear Cells and Platelet-Rich Plasma. Plast Reconstr Surg Glob Open. 2017 Jun 29;5(6):e1376. doi: 10.1097/GOX.0000000000001376. PMID: 28740784; PMCID: PMC5505845.
  Single patient treated with bell’s palsy treated with plasma blood mononuclear cells and PRP locally injected along the distribution of the affected facial nerve. Treatment was repeated 9 times within a year. After completion of the regimen, the patient had significant improvement in the voluntary motion of facial muscles. There was significant improvement in facial contouring and the facial asymmetry was significantly reduced. She was able to completely close her left eye and 80% close her right eye. Plasma blood mononuclear cells and PRP demonstrated significant improvement in facial spasticity associated with bell’s palsy.

Cerebral palsy

• Effect of Autologous Cord Blood Infusion on Motor Function and Brain Connectivity in Young Children with Cerebral Palsy: A Randomized, Placebo-Controlled Trial
  63 patients diagnosed with CP were enrolled in Dr. Sun’s study. These patients were randomized to receive ACB (N=32) or placebo (N=31) and then there was a crossover between infusions at 1 year. These patients were further stratified into high infused cell dose (>2x10^7 total nucleated cells) or low infused cell dose (<2x10^7 total nucleated cells) and they received these doses intravenously. When comparing the experimental and placebo groups, there was no significant difference in the Gross motor function measure (GMFM) at 1 year. When stratifying based off infusion dose, the group receiving the high dose infusion demonstrated statistically significant improvement in GMFM at 1 year (+4.3), compared to low dose (-1.9) and placebo (+2.2). The patients who received the high dose infusion also demonstrated statistically significant improvement in normalized whole brain connectivity. Both of these findings were demonstrated again after the crossover of patients occurred at 1 year after protocol initiation. This study suggests a dose dependent relationship in treating CP with autologous cord blood intravenously. Greater than 2x10^7 total nucleated cells was associated with improved gross motor scores and improved whole brain connectivity at 1 year. The low dose group did not show improvement compared to placebo.
• Umbilical Cord Blood Therapy Potentiated with Erythropoietin for Children with Cerebral Palsy: A Double-blind, Randomized, Placebo-Controlled Trial
  In Dr. Min’s study, 96 patients with CP were enrolled and split into three cohorts. Group one received at least 3x10^7/kg total nucleated cells of allogeneic umbilical cord blood intravenously with two doses of 500 IU/kg recombinant human EPO, group 2 received 500 IU/kg EPO only and group 3 received placebo. The group receiving the allogeneic umbilical cord blood demonstrated statistically significant improvement compared to the other two groups in Gross Motor Performance Measure and BSID-II Mental and Motor scores at 3 and 6 months after treatment.   At 6 months the mean difference in GMPM between the allogeneic umbilical cord group was 5.34 and 4.95 when compared to the EPO and control groups, respectively. This study demonstrates that intravenous allogeneic umbilical cord cells at a dose of 3x10^7 total nucleated cells when combined with EPO showed significant improvement in gross motor ratings at 3 and 6 months; EPO alone was ineffective.
• A Randomized, Placebo-Controlled Trial of Human Umbilical Cord Blood Mesenchymal Stem Cell Infusion for Children With Cerebral Palsy
  Dr. Huang’s trial consisted of 54 patients with cerebral palsy who were split into two groups. Group one received 4 infusions, each consisting of 5x10^7 human umbilical cord blood mesenchymal stem cells intravenously and group two received placebo (.9% NS).  Statistically significant improvement was seen in the experimental group compared to the control group in the GMFM-88 at 3, 6, 12 and 24 months. By the three month follow up, the experimental group demonstrated improvement in all 5 parameters (lying, sitting, crawling, standing and walking). The change in total score proportion in GMFM-88  was 10.27 in the experimental group vs. 4.75 for the control group at the end of 1 year. The experimental group also demonstrated significant improvement compared to control on the Comprehensive Functional Assessment (CFA) at 3, 6, 12 and 24 months. The change in total score in CFA was 18.9 in the experimental group vs. 8.07 in the control group at the end of one year.  Repeat intravenous infusions of umbilical cord mesenchymal stem cells at a dose of 5x10^7 resulted in significant gross motor and comprehensive functional assessment improvement compared to placebo at 1 year.
• Therapeutic evidence of umbilical cord-derived mesenchymal stem cell transplantation for cerebral palsy: a randomized, controlled trial
  Dr. Gu’s trial consisted of 39 patients with cerebral palsy. 19 of the patients received four doses of 5x10^7 human umbilical cord mesenchymal stem cells intravenously along with standard physical therapy. The other 20 patients received 50ml of NS with 1% human serum albumin along with standard therapy. The experimental group demonstrated statistically significant improvement in ADL compared to the control group at 3 (+12.4 vs +5.97), 6 (+21.1 vs +10.1) and 12 (+23.0 vs +12.8) months. Additionally, there were significant differences between groups in the comprehensive functional assessment at 3 (+17.9 vs +7.4) and 6 (+23.8 vs +11.9) months. The gross motor functional measure improvement significantly differed at 6 (+59.0 vs +28.9) and 12 (+ 64.5 vs +36.8) months.  Repeat intravenous infusions of umbilical cord mesenchymal stem cells at a dose of 5x10^7 resulted in significant improvement in ADL, comprehensive functional assessment and gross motor compared to placebo at 12 months.
• Comparative analysis of curative effect of bone marrow mesenchymal stem cell and bone marrow mononuclear cell transplantation for spastic cerebral palsy
  Dr. Liu enrolled 105 patients with cerebral palsy and these patients were divided into three groups. Group 1 received cultured autologous Bone marrow mesenchymal stem cells, group 2 received autologous bone marrow mononuclear cells and group three only received standard therapy. For the first two groups, the patients received four cell transplants, each cultured and consisting of 1x10^6 cells intrathecally. At 6 and 12 months, GMFM demonstrated significant improvement in the BMSC group compared to the other two groups. At 12 months, the GMFM was 127, 111 and 102 for the BMSC, BMMNC and control groups, respectively.  Additionally, at 6 and 12 months, the BMSC group demonstrated significant difference from the other 2 groups in fine motor functional measurement. The FMFM scores after 12 months were 79, 53 and 8 for the BMSC, BMMNC and control groups, respectively.  Repeat intrathecal injection of 1x10^6 autologous bone marrow derived mesenchymal stem cells showed significant improvement at 1 year in gross motor and fine motor ratings compared to patients who received the same dose of bone marrow derived mononuclear cells and control groups.
• Outcomes of autologous bone marrow mononuclear cells for cerebral palsy: an open label uncontrolled clinical trial
  In Dr. Nguyen’s study, 40 patients with cerebral palsy were treated with two doses of bone marrow mononuclear cells injected intrathecally. The first treatment consisted of 27.2 x 10^ 6 mononuclear cells and 2.6x10^6 CD34+ cells. The second treatment three months later contained 17.1x10^6  mononuclear cells and 1.7x10^6 CD34+ cells. Patients demonstrated statistically significant improvement at 3 months and 6 months in all the parameters if the GMFM-88 and the modified ashworth score. The average GMFM-88 was 16.7 at baseline and increased to 38.9 at 3 months and 41.8 6 months after transplantation. The Modified ashworth score decreased from an average of 3.4 at baseline to 2.1 at 3 months and 2.0 after 6 months. Repeat intrathecal injection of bone marrow mononuclear cells demonstrated significant improvement in motor function and measures of spasticity at 6 months when compared to baseline.
• Improvement in gross motor function and muscle tone in children with cerebral palsy related to neonatal icterus: an open-label, uncontrolled clinical trial
  In Dr. Thanh’s study, 25 patients were treated with intrathecal autologous bone marrow aspirate mononuclear cells in an attempt to treat cerebral palsy.  The patients received 17.4x10^6  mononuclear cells and 1.5x10^6 CD34+ cells in the first treatment and 6 months later in the second treatment received 15x10^6 and 1.1x10^6, respectively. All parameters of the GMFM-88 improved significantly at both 6 months and at 12 months. The overall average GMFM-8 at baseline was 18.3. This increased to 35.8 after 6 months and 53.2 after 12 months. The ashworth score also improved significantly 6 months and 12 months post-transplantation.  The initial Ashworth score was 4.0 at baseline and decreased to 3.3 after 6 months and 3.0 after 12 months. Repeat intrathecal injection of bone marrow mononuclear cells demonstrated significant improvement in motor function and measures of spasticity at 6 and 12 months when compared to baseline.
• Treatment of Cerebral Palsy with Stem Cells: A Report of 17 Cases
  17 patients with CP were enrolled in this study. Each patient received roughly two million bone marrow mononuclear cells per kilogram of body weight intrathecally. Progress was determined by the Gross Motor Function Classification Scale (GMFCS). 11/15 patients demonstrated an improvement of GMFCS, with an overall average increase of 1.3 points. None of the patients regressed on this scale during the study period. There was also a cognitive function assessment, for which 40% of the patient population demonstrated improvement throughout the study period.  Intrathecal injection of bone marrow mononuclear cells at a dose of two million per kilogram demonstrated improvement in gross motor and comprehensive function assessment compared to baseline.

Click here for the clinical trial for Cerebral Palsy

Chronic Obstructive Pulmonary Disease

• Stolk J, Broekman W, Mauad T, Zwaginga JJ, Roelofs H, Fibbe WE, Oostendorp J, Bajema I, Versteegh MI, Taube C, Hiemstra PS. A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema. QJM. 2016 May;109(5):331-6. doi: 10.1093/qjmed/hcw001. Epub 2016 Jan 27. PMID: 26819296; PMCID: PMC4888332.
  7 patients with severe emphysema were treated with 2 doses of cultured bone marrow derived mesenchymal stem cells intravenously, each 1 week apart. After 12 months, FEV1 showed significant improvement (average increase 390mL). Also a significant improvement in CT derived lung density after 1 year. Intravenous cultured bone marrow mesenchymal stem cells demonstrated improvement after 1 year in FEV1 and lung density.  
• Le Thi Bich P, Nguyen Thi H, Dang Ngo Chau H, Phan Van T, Do Q, Dong Khac H, Le Van D, Nguyen Huy L, Mai Cong K, Ta Ba T, Do Minh T, Vu Bich N, Truong Chau N, Van Pham P. Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study. Stem Cell Res Ther. 2020 Feb 13;11(1):60. doi: 10.1186/s13287-020-1583-4. PMID: 32054512; PMCID: PMC7020576.
  20 patients with COPD were treated with cultured allogeneic umbilical cord mesenchymal stem cells, administered intravenously. Modified Medical Research Council score, COPD Assessment Test and number of exacerbations significantly improved after 6 months. No change in CRP, FEV1 or 6MWT. Intravenous cultured umbilical mesenchymal stem cells demonstrated improvement in quality of life indexes and number of exacerbations up to 6 months after treatment.

Diabetes

• Hu J, Yu X, Wang Z, Wang F, Wang L, Gao H, Chen Y, Zhao W, Jia Z, Yan S, Wang Y. Long term effects of the implantation of Wharton's jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus. Endocr J. 2013;60(3):347-57. doi: 10.1507/endocrj.ej12-0343. Epub 2012 Nov 16. PMID: 23154532.

Dr. Hu’s clinical trial enrolled 29 patients with type 1 diabetes, 15 of which were treated and 14 were used as controls. The patients randomized to the experimental group received an average of 2.6x10^7 of cultured Wharton’s Jelly Mesenchymal Stem Cells intravenously.  From 9 months to 24 months, the experimental group demonstrated statistically significant improvement in postprandial glucose levels compared to the control group.  Additionally, the experimental group demonstrated statistically significant improvement compared to the control group from 9 to 24 months after treatment in HgbA1c levels. At the end of the follow up period, 11/15 patients in the experimental group either no longer required insulin therapy or had a dose reduction greater than 50%. In the control group, 7/14 required a dose increase greater than 50% at the end of the trial period compared to baseline. Intravenous cultured wharton’s jelly mesenchymal stem cells at a dose of 2.6x10^7 demonstrated significant improvement compared to the control group at the end of the 24 month study period in postprandial glucose levels, HgbA1c levels and in reduction of daily insulin requirements.   

• Jiang R, Han Z, Zhuo G, Qu X, Li X, Wang X, Shao Y, Yang S, Han ZC. Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med. 2011 Mar;5(1):94-100. doi: 10.1007/s11684-011-0116-z. Epub 2011 Mar 17. PMID: 21681681.

Dr. Jiang’s clinical trial enrolled 10 patients with type 2 diabetes. They were treated with 3 doses with a one month interval between treatments with a total of 1.35x10^6 placenta derived mesenchymal stem cells per kg intravenously. All patients were followed for 3 months. A daily mean dose of insulin was reduced from 63.7 to 34.7 and 4/10 patients had a reduction of >50% of daily insulin usage. The average C-peptide for the 10 patients was increased from 4.1 to 5.6. Repeat treatment of 1.35x10^6/kg of placenta derived mesenchymal stem cells administered intravenously demonstrated significant improvement in reduction of daily insulin requirement and average C-peptide level for at least 3 months.

• Cai J, Wu Z, Xu X, Liao L, Chen J, Huang L, Wu W, Luo F, Wu C, Pugliese A, Pileggi A, Ricordi C, Tan J. Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion. Diabetes Care. 2016 Jan;39(1):149-57. doi: 10.2337/dc15-0171. Epub 2015 Dec 1. PMID: 26628416.

Dr. Cai’s clinical enrolled 42 patients with type 1 diabetes. 21 patients were allocated to the experimental group and 21 patients were assigned to the control group. The treated group was given 1.1x10^6 cultured umbilical cord cells per kilogram and 106.8x10^6 bone marrow mononuclear cells per kilogram, administered directly into the dorsal pancreatic artery. After 12 months, the AUC-Cpeptide increased 105.7% in the experimental group (6.6 to 13.6). The AUC-cpeptide decreased 7.7% in the control group (8.4 to 7.7). The AUC-Insulin increased 49.3% in the experimental group (1477 to 2205), while decreasing 5.7% in the control group (1517 to 1431). HgbA1c decreased 12.6% in the experimental group (8.6 to 7.5) while it increased 1.2% in the control group (8.7 to 8.8).  Infusion of 1.1x10^6 cultured umbilical cord cells combined with 106.8x10^6 bone marrow mononuclear cells per kilogram directly into the dorsal pancreatic artery showed significant improvement of C-peptide, endogenous insulin production and HgbA1c after 12 months compared to control group.

• Mesples, A. , Zhang, Y. and Hu, X. (2020) Long Term Benefit of Autologous Bone Marrow Stem Cell Transplantation without Immunosuppression in Chronic Type 1 Diabetic Patients. Stem Cell Discovery, 10, 1-14. doi: 10.4236/scd.2020.101001.

Dr. Mesples study enrolled 134 patients diagnosed with Type 1 DM. The patients received 5 - 10 mg/kg/day of filgrastim subcutaneously for 4 days. On the 5^th day bone marrow was aspirated, no culturing occurred. The patients received  CMN > 1 × 120 and CD34+ > 0.37 × 10.6/kg intravenously. At onset of the study, all 134 patients had c-peptide levels less than .5ng/ml. At one year follow up, 34 patients had c-peptides below .5ng/ml, 50 patients had c-peptides between .5 and .9ng/ml and 50 patients had c-peptides above .9ng/ml. Initially, 28 patients were receiving greater than 40 units of Insulin daily and there weren’t any patients were receiving no insulin. After 1 year, only 3 patients were receiving more than 40 units and 60 patients were receiving no insulin. Initially, only 25 patients had A1c levels less than 7 and 21 patients had A1c levels above 9. After 1 year, 90 patients had A1c levels less than 7 and only 3 patients had A1c levels above 9. Filgastrim treatment followed by bone marrow aspiration and intravenous reinfusion demonstrated the ability to significantly increase c-peptide levels, decrease total insulin requirement and significantly improve HgbA1c levels 1 year after treatment.

• Bhansali, S., Dutta, P., Kumar, V., Yadav, M. K., Jain, A., Mudaliar, S., Bhansali, S., Sharma, R. R., Jha, V., Marwaha, N., Khandelwal, N., Srinivasan, A., Sachdeva, N., Hawkins, M., & Bhansali, A. (2017). Efficacy of Autologous Bone Marrow-Derived Mesenchymal Stem Cell and Mononuclear Cell Transplantation in Type 2 Diabetes Mellitus: A Randomized, Placebo-Controlled Comparative Study. Stem cells and development, 26(7), 471–481. https://doi.org/10.1089/scd.2016.0275

Dr. Bhansali’s study enrolled 30 patients diagnosed with type 2 diabetes. 10 patients were treated with 1 million autologous bone marrow derived mesenchymal stem cells per kilogram and 10 patients were treated with about 1 billion autologous bone marrow mononuclear cells. Both of these cell loads were infused directly into the superior pancreaticoduodenal artery. An additional 10 patients underwent a sham procedure. The primary endpoint was a reduction in insulin requirement by greater than 50% from baseline, while maintaining HbA1c <7.0%. Both of the experimental had 60% of patients reach the primary endpoint, while the control group had 0% reach the primary endpoint. Injection into superior pancreaticoduodenal artery of bone marrow mononuclear cells and bone marrow mesenchymal stem cells demonstrated superior efficacy in reducing insulin requirement while maintaining a low HgbA1c compared to placebo 1 year after treatment.  

• Liu X, Zheng P, Wang X, Dai G, Cheng H, Zhang Z, Hua R, Niu X, Shi J, An Y. A preliminary evaluation of efficacy and safety of Wharton's jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cell Res Ther. 2014 Apr 23;5(2):57. doi: 10.1186/scrt446. PMID: 24759263; PMCID: PMC4055092.

Dr. Liu’s study enrolled 22 patients with T2DM. The patients received two doses of Wharton’s Jelly Mesenchymal Stem Cells, each at a dose of one million cells per kilogram body weight. The first dose was delivered intravenously and the second dose, 5 days later, was delivered into the splenic artery. HgbA1c showed significant improvement at 1 month, 3 months, 6 months and 1 year after treatment. Baseline HgbA1c average was 8.2 and the average was 7.0 at 12 month follow up. 2 hour postprandial glucose also demonstrated significant improvement at 1, 3, 6 and 12 months after treatment. Baseline postprandial glucose was 14.96 and this decreased to 12.25 at 12 months. Additionally, the patients receiving Insulin therapy showed a statistically significant dose reduction at 1, 3, 6 and 12 months compared to baseline. Wharton’s Jelly mesenchymal stem cells demonstrated significant improvement in HgbA1c, postprandial glucose levels and insulin dose requirement at 1, 3, 6 and 12 months when compared to baseline.

Click here for the clinical trial for Diabetes

Erectile dysfunction and Peyronie's Disease

• Bahk JY, Jung JH, Han H, Min SK, Lee YS. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp Clin Transplant. 2010 Jun;8(2):150-60. PMID: 20565373.
  7 patients with T2DM who suffer from ED were included and treated with allogeneic human umbilical mesenchymal stem cells. They received injections into bilateral corpus cavernosa. The penile root was clamped and released 30 after the injection. After 2 months, 6/7 patients reported increased penile hardness, however, this increased hardness was still insufficient for penetration. 2/7 were able to achieve effective penetration, maintenance and orgasm 3 months post injection with the addition of PDE-5 inhibitor. Only 1 of these 2 patients maintained this effect beyond 9 months. At the 11 month follow up, 2 of the participants received prosthesis, 1 returned to complete non-erectile status, 3 could only achieve poor erections and 1 was able to maintain erection sufficient for coitus with assistance of PDE-5 inhibitor. Human umbilical cord mesenchymal stem cells directly into corpus cavernosum showed improvement in hardness in most patients at 2 months. 2 patients were able to have intercourse and orgasm 3 months after injection, 1 patient maintained effect at 11 months.  
• Garber MG and Carlos ND. Intracavernous administration of adipose stem cells: a new technique of treating erectile dysfunction in diabetic patient, preliminary report of 6 cases. MOJ Cell Sci Rep. 2015;2(1):5-8.
  6 patients with T2DM suffering from ED were enrolled in this study. Only patients with BMI between 19-23 were enrolled in this study. Adipose cells were acquired via stromal vascular fragment. Cells were injected into bilateral corpus cavernosum. The penile root was clamped prior to the injection and released 30 minutes after. With the addition of PDE-5 inhibitor, 5 could achieve penetration, maintenance and orgasm and retained this at six months after treatment. At 12 month follow up, 4 of the 6 retained these abilities. SVF into corpus cavernosum showed improvement in penile hardness. 6 and 12 months after treatment majority of patients demonstrated ability to have intercourse when supplemented with PDE-5 inhibitors.
• Haahr MK, Jensen CH, Toyserkani NM, Andersen DC, Damkier P, Sørensen JA, Lund L, Sheikh SP. Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial. EBioMedicine. 2016 Jan 19;5:204-10. doi: 10.1016/j.ebiom.2016.01.024. PMID: 27077129; PMCID: PMC4816754.
  21 patients with ED after radical prostatectomy were enrolled in this study. SVF was injected into bilateral corpus carvernosum  at 2 bilateral points in the distal and proximal parts of the corpus cavernosum. A tourniquet was applied to the base of the penis and removed 30 minutes after the injection.  8 of the 21 participants recovered erection sufficient for intercourse in the 12 month observation time. 3 of these 8 did not need medication assistance.  Including all 21 patients, the International Index of Erectile Function did not show statistically significant improvement. When looking only at the 14 patients who were continent prior to onset of the trial, these patients had an International index of erectile function significant at 6 months and were sustained at 12 months. SVF injected directly into corpus cavernosum. About half patients suffering from ED after radical prostatectomy were able to sustain erection for intercourse 12 months after treatment. International index of erectile function was dependent on if patients were continent prior to treatment, with significant improvement in those who were continent. 
• Protogerou V, Michalopoulos E, Mallis P, et al. Administration of Adipose Derived Mesenchymal Stem Cells and Platelet Lysate in Erectile Dysfunction: A Single Center Pilot Study. Bioengineering (Basel). 2019;6(1):21. Published 2019 Mar 5. doi:10.3390/bioengineering6010021
  This study included 8 patients who suffer from ED. 5 patients were placed in Group A and they received 3.8x10^7 ADMSC along with 2.2mL PL into the corpus cavernosum. 3 patients were placed in group B and received 2.3mL of PL into the corpus cavernosum. 4 of the 5 patients in group A demonstrated improved IIEF after 1 month and after 3 months. All three patients in group B showed improvement in IIEF after the first and third month.   Statistically significant difference was observed in IIEF-5 score for both groups before and after administration. No statistically significant difference was observed in IIEF-5 score between patients of group A and B. Both combined ADMSC and PL and PL alone directly into corpus cavernosum demonstrated significant improvement in IIEF after 1 and 3 months.
• Protogerou V, Beshari SE, Michalopoulos E, Mallis P, Chrysikos D, Samolis AA, Stavropoulos-Giokas C, Troupis T. The Combined Use of Stem Cells and Platelet Lysate Plasma for the Treatment of Erectile Dysfunction: A Pilot Study-6 Months Results. Medicines (Basel). 2020 Mar 18;7(3):14. doi: 10.3390/medicines7030014. PMID: 32197323; PMCID: PMC7151592.
  5 patients with ED secondary to various causes were treated in this study.  ADMSC were injected directly into the corpus cavernosum.  All patients showed improvement in IIEF by the 6^th month follow up visit. Two of the five patients developed unassisted hard erections by the 3^rd month follow up. The other 3 patients were able to develop hard erections on oral PDE-5 inhibitors by the 3 month follow up. One of the patients was suffering from ED secondary to Peyronie’s disease. Initial IIEF for this patient was 14 at baseline and increased to 21 at 6 months. Initially only moderate erections with intracavernosal injections and after 6 months had unassisted hard erections. Treated with ADMSC injected into corpus carvenosum. All 5 patients showed improvement in IIEF by 6 months. All were able to have hard erections with or without PDE-5 by 3 month follow up. Patient with Peyronie’s disease showed improvement consistent with remainder of group.
• Al Demour S, Jafar H, Adwan S, AlSharif A, Alhawari H, Alrabadi A, Zayed A, Jaradat A, Awidi A. Safety and Potential Therapeutic Effect of Two Intracavernous Autologous Bone Marrow Derived Mesenchymal Stem Cells injections in Diabetic Patients with Erectile Dysfunction: An Open Label Phase I Clinical Trial. Urol Int. 2018;101(3):358-365. doi: 10.1159/000492120. Epub 2018 Aug 31. PMID: 30173210.
  4 patients with ED secondary to DM were included in study. Patients treated with autologous derived bone marrow derived mesenchymal stem cells administered by bilateral injection into corpus cavernosum. Patients were followed by 12 months. At the end of the study follow up, there was significant improvement in International Index of Erectile Function, erectile hardness score and sexual desire. Treated with autologous bone marrow derived mesenchymal stem cells into the corpus cavernosum. Showed significant improvement after 12 months in erectile function, erectile hardness and sexual desire.

Eye disease

• Zhang X, Liu J, Yu B, Ma F, Ren X, Li X. Effects of mesenchymal stem cells and their exosomes on the healing of large and refractory macular holes. Graefes Arch Clin Exp Ophthalmol. 2018 Nov;256(11):2041-2052. doi: 10.1007/s00417-018-4097-3. Epub 2018 Aug 30. PMID: 30167916.
  7 patients with long standing idiopathic macular holes were enrolled in this study. All patients underwent vitrectomy and internal limiting membrane peeling. Two patients then received intravitreal mesenchymal stem cells injection and 5 patients underwent mesenchymal stem cell derived exosome intravitreal injection. 6 macular holes closed and one remained open. BCVA was improved in five patients. Intravitreal injection of mesenchymal stem cells or mesenchymal stem cell derived exosomes in patients with idiopathic macular holes resulted in hole closure and increased visual acuity.
• Sung Y, Lee SM, Park M, Choi HJ, Kang S, Choi BI, Lew H. Treatment of traumatic optic neuropathy using human placenta-derived mesenchymal stem cells in Asian patients. Regen Med. 2020 Oct;15(10):2163-2179. doi: 10.2217/rme-2020-0044. Epub 2020 Dec 14. PMID: 33315474.
  4 Asian patients suffering from traumatic optic neuropathy were enrolled in this study. The patients were treated with subtenon transplantation of human placenta derived mesenchymal stem cells. When reassessed 12 months after treatment, Tuj1 and Gfap expression was significantly higher in the treatment group than the sham group. This suggests a protective effect on the optic nerve and retinal ganglion cells. All 4 patients demonstrated improved visual acuity. Subtenon transplantation of human placenta derived mesenchymal stem cells administered to patients with traumatic optic neuropathy demonstrated improved protective effect on the optic nerve and retinal ganglion cells along with improved visual acuity when assessed 12 months after treatment.
• Takagi S, Mandai M, Gocho K, Hirami Y, Yamamoto M, Fujihara M, Sugita S, Kurimoto Y, Takahashi M. Evaluation of Transplanted Autologous Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in Exudative Age-Related Macular Degeneration. Ophthalmol Retina. 2019 Oct;3(10):850-859. doi: 10.1016/j.oret.2019.04.021. Epub 2019 Apr 26. PMID: 31248784
  Single patient was enrolled in this study who was diagnosed with exudative age related macular degeneration and polypoidal choroidal vasculopathy. Patient was treated with an induced pluripotent stem cell derived retinal pigmented epithelium sheet. At 4 year follow up, the sheet had survived beneath the retina. Visual acuity remained stable with no additional injections of anti-VEGF medication. The sheet had demonstrated the ability to support photoreceptors and choroid vessels. Induced pluripotent stem cell derived retinal pigmented epithelium sheet administered to a patient with exudative age related macular degeneration and polypoidal choroidal vasculopathy demonstrated sheet survival, stable visual acuity and support for photoreceptors and choroid vessels when reassessed 4 years after implantation.
• Schwartz SD, Regillo CD, Lam BL, Eliott D, Rosenfeld PJ, Gregori NZ, Hubschman JP, Davis JL, Heilwell G, Spirn M, Maguire J, Gay R, Bateman J, Ostrick RM, Morris D, Vincent M, Anglade E, Del Priore LV, Lanza R. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet. 2015 Feb 7;385(9967):509-16. doi: 10.1016/S0140-6736(14)61376-3. Epub 2014 Oct 15. PMID: 25458728.
  This study enrolled 9 patients with atrophic age related macular degeneration and 9 patients with Stargardt macular dystrophy. Patients were treated with human embryonic stem cell derived retinal pigmented epithelium. The patients were split into 3 cohorts receiving either 50,000 cells, 100,000 cells or 150,000 cells administered subretinally. The patients were followed for a median of 22 months. 72% of patients had patches of increasing subretinal pigmentation. 10 eyes showed significantly improved BCVA, 7 eyes showed minimal change or stable BCVA and 1 eye showed significant worsening of BCVA. Untreated control eyes did not show any improvements in visual acuity. Subretinal transplantation of human embryonic stem cell derived retinal pigmented epithelium in patients with AMD and Stargardt macular dystrophy resulted in increased subretinal pigmentation and improved visual acuity scores.
• Christopher D Riemann, Eyal Banin, Adiel Barak, David S Boyer, Rita Ehrlich, Tareq Jaouni, Richard McDonald, David Telander, Michael Keane, Jessica Ackert, Mark D. Ferguson, Avi Ben- Shabat, Jordi Mones, Diana Angelini, Gary S. Hogge, Benjamin Reubinoff; Phase I/IIa Clinical Trial of Human Embryonic Stem Cell (hESC)-Derived Retinal Pigmented Epithelium (RPE, OpRegen) Transplantation in Advanced Dry Form Age-Related Macular Degeneration (AMD): Interim Results. Invest. Ophthalmol. Vis. Sci. 2020;61(7):865.
  4 patients with dry age related macular degeneration were included in this study. Patients were treated with retinal pigmented epithelium derived from human embryonic stem cells. Cells were transplanted subretinal. Visual acuity improvement was noted in all 4 patients and the improvement ranged from 10-22 letters. The improvement was first seen at 4.5 months and maintained to over 15 months. Patients also demonstrated alterations in drusen appearance, subretinal pigmentation and hyper-reflective areas, all indicative of the presence of transplanted RPE cells. Subretinal implantation of RPE derived from human embryonic stem administered to patients with D-AMD demonstrated significant improvement in visual acuity from 4-15 months. Additionally, there were alterations in drusen appearance, subretinal pigmentation and hyper-reflective areas.
• Oner A, Gonen ZB, Sevim DG, Smim Kahraman N, Unlu M. Suprachoroidal Adipose Tissue-Derived Mesenchymal Stem Cell Implantation in Patients with Dry-Type Age-Related Macular Degeneration and Stargardt's Macular Dystrophy: 6-Month Follow-Up Results of a Phase 2 Study. Cell Reprogram. 2018 Dec;20(6):329-336. doi: 10.1089/cell.2018.0045. PMID: 31251672.
  This study included 4 patients with dry age related macular degeneration and 4 patients with Stargardt macular dystrophy. Patients were treated with suprachoroidal adipose tissue derived mesenchymal stem cells. When reassessed 6 months after treatment, all patients experienced visual acuity improvement, visual field improvement and improvement in mf-ERG recordings. Adipose derived mesenchymal stem cells administered suprachoroidal in patients with D-AMR and Stargardt macular dystrophy demonstrated improvements in visual acuity, visual field and mf-ERG recordings when reassessed 6 months after treatment.
• Song WK, Park KM, Kim HJ, Lee JH, Choi J, Chong SY, Shim SH, Del Priore LV, Lanza R. Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients. Stem Cell Reports. 2015 May 12;4(5):860-72. doi: 10.1016/j.stemcr.2015.04.005. Epub 2015 Apr 30. PMID: 25937371; PMCID: PMC4437471
  4 patients were included in this study. All patients were Asian. Two patients suffered from dry age related macular degeneration and two patients suffered from Stargardt macular dystrophy. Patients were treated with subretinal transplantation of human embryonic stem cell derived retinal pigment epithelium. After 1 year, 3 of the patients developed significant improvement in visual acuity, improving between 9-19 letters. The other one patient increased 1 letter on visual acuity and was remaining stable. Subretinal transplantation of human embryonic stem cell derived retinal pigment epithelium in patients with dry age related macular degeneration and Stargardt macular dystrophy resulted in improved visual acuity when reassessed 1 year after treatment.
• Wiącek MP, Gosławski W, Grabowicz A, Sobuś A, Kawa MP, Baumert B, Paczkowska E, Milczarek S, Osękowska B, Safranow K, Zawiślak A, Lubiński W, Machaliński B, Machalińska A. Long-Term Effects of Adjuvant Intravitreal Treatment with Autologous Bone Marrow-Derived Lineage-Negative Cells in Retinitis Pigmentosa. Stem Cells Int. 2021 Jun 2;2021:6631921. doi: 10.1155/2021/6631921. PMID: 34122558; PMCID: PMC8192192.
  30 eyes with retinitis pigmentosa were included in this study. Patients received cultured autologous bone marrow derived mesenchymal stem cells administered via intravitreal injection. When reassessed 1 year after treatment, average visual acuity significantly increased. Contrast sensitivity also improved significantly 1 year after treatment. Additionally, visual field deviation also improved significantly at 12 month follow up. Cultured autologous bone marrow derived mesenchymal stem cells administered intravitreal demonstrated significant improvement in visual acuity, contrast sensitivity and visual field deviation in patients with retinitis pigmentosa when reassessed 1 year after treatment.   
• Özmert E, Arslan U. Management of retinitis pigmentosa by Wharton's jelly derived mesenchymal stem cells: preliminary clinical results. Stem Cell Res Ther. 2020 Jan 13;11(1):25. doi: 10.1186/s13287-020-1549-6. PMID: 31931872; PMCID: PMC6958670.
  This study enrolled 32 patients (34 eyes) diagnosed with retinitis pigmentosa. The patient were treated with cultured wharton’s jelly mesenchymal stem cells injected into the subtenon space. The average BCVA improved from 70.5 letters pretreatment to 80.6 6 months post-treatment. The mean visual field median deviation improved from 27.3 pretreatment to 24.7 6 months after treatment. The average outer retinal thickness was 100.3 pretreatment and this improved to an average of 119.1 after treatment. Wharton’s jelly mesenchymal stem cells injected into the subtenon space in patients with retinitis pigmentosa resulted in improved visual acuity, improved visual field deviation and increased outer retinal thickness when reassessed 6 months after treatment.
• Limoli PG, Limoli C, Vingolo EM, Franzone F, Nebbioso M. Mesenchymal stem and non-stem cell surgery, rescue, and regeneration in glaucomatous optic neuropathy. Stem Cell Res Ther. 2021 May 6;12(1):275. doi: 10.1186/s13287-021-02351-4. PMID: 33957957; PMCID: PMC8101217.
  25 patients (35 total eyes) diagnosed with glaucomatous optic neuropathy were enrolled in this study. 21 eyes were used as controls and 14 eyes received suprachoroidal autograft of SVF mesenchymal stem cells and platelets from PRP. 6 months after treatment, visual acuity, close-up visus and microperimetric sensitivity was significantly increased in the experimental group, whereas there were no significant improvements in the control group. Suprachoroidal autograft of SVF mesenchymal stem cells with platelets from PRP administered to the suprachoroidal region in patients with glaucomatous optic neuropathy demonstrated significantly improved visual acuity, close up visus and microperimetric sensitivity. Control showed no significant improvement.  
• Kahraman NS, Oner A. Umbilical cord derived mesenchymal stem cell implantation in retinitis pigmentosa: a 6-month follow-up results of a phase 3 trial. Int J Ophthalmol. 2020;13(9):1423-1429. Published 2020 Sep 18. doi:10.18240/ijo.2020.09.14
  This study enrolled 82 patients (124 total eyes) diagnosed with retinitis pigmentosa. The patients were treated with 5 million umbilical cord derived mesenchymal stem cells administered to the suprachoroidal area with a surgical procedure. At 6 month follow up, there was significant improvement in visual acuity and visual fields. Suprachoroidal administration of umbilical cord derived mesenchymal stem cells in patients with retinitis pigmentosa demonstrated improvements in visual acuity and visual field when reassessed 6 months after treatment.
• da Cruz L, Fynes K, Georgiadis O, Kerby J, Luo YH, Ahmado A, Vernon A, Daniels JT, Nommiste B, Hasan SM, Gooljar SB, Carr AF, Vugler A, Ramsden CM, Bictash M, Fenster M, Steer J, Harbinson T, Wilbrey A, Tufail A, Feng G, Whitlock M, Robson AG, Holder GE, Sagoo MS, Loudon PT, Whiting P, Coffey PJ. Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. Nat Biotechnol. 2018 Apr;36(4):328-337. doi: 10.1038/nbt.4114. Epub 2018 Mar 19. PMID: 29553577.
  Two patients with severe age related macular degeneration were enrolled in this study. Both patients were treated with a retinal pigmented epithelium patch comprised of human embryonic stem cells. The patch was administered subretinal. The two patients had an increase in visual acuity of 29 letters and 21 letters when reassessed 12 months after treatment. The administration of a retinal pigmented epithelium patch derived from human embryonic stem cells for patients with severe age related macular degeneration increased visual acuity significantly after 1 year.
• Efficacy and Safety of Autologous Bone Marrow Mesenchymal Stem Cell Transplantation in Patients with Diabetic Retinopathy Xianliang Gua,b Xi Yua,b Chen Zhaoa,b Ping Duana,b Tongtao Zhaoa,b Yong Liua,b Shiying Lia,b Zhi Yangc Yunyan Lic Cheng Qianc Zhengqin Yina,b Yi Wanga,b
  34 total eyes (17 patients) with diabetic retinopathy were recruited for this study. Patients were treated with a single intravenous infusion of cultured autologous bone marrow derived mesenchymal stem cells. Patients with a diagnosis of Nonproliferative diabetic retinopathy demonstrated significant macular thickness reduction and BCVA when reassessed 3 and 6 months after treatment. Patients diagnosed with proliferative diabetic retinopathy did not demonstrate same improvement. Cultured autologous bone marrow derived mesenchymal stem cells demonstrated significant reduction in macular thickness and improvements in BCVA at 3 and 6 months for patients with NPDR. Patients with PDR did not demonstrate significant improvement.
•  Weiss JN, Levy S, Benes SC. Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a case report of improvement in relapsing auto-immune optic neuropathy. Neural Regen Res. 2015 Sep;10(9):1507-15. doi: 10.4103/1673-5374.165525. PMID: 26604914; PMCID: PMC4625519.
  This study includes a single 54 year old female suffering from relapsing optic neuritis. The patient underwent a vitrectomy and intra-optic nerve injection of autologous bone marrow derived mesenchymal stem cells in the right eye. She also received retrobulbar, subtenon and intravitreal injection of BMSCs. Pretreatment visual acuity measure 20/400 in the right eye and 20/70 in the left eye. 15 months after treatment, her visual acuity was 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved significantly. The patient was able to decrease her mycophenylate from 1500mg per day to 500mg per day and required no steroid pulse therapy during the 15 month study period. Autologous bone marrow derived mesenchymal stem cells administered intra-optic nerve, retrobulbar, subtenon and intravitreal for auto-immune optic neuritis demonstrated significant improvement at 15 months in visual acuity, visual fields and medication requirement when compared to baseline.  
• Weiss JN, Benes SC, Levy S. Stem Cell Ophthalmology Treatment Study (SCOTS): improvement in serpiginous choroidopathy following autologous bone marrow derived stem cell treatment. Neural Regen Res. 2016 Sep;11(9):1512-1516. doi: 10.4103/1673-5374.191229. PMID: 27857759; PMCID: PMC5090858.
  This study includes a single 77 year old male suffering from long standing serpiginous choroidopathy. The patient was treated with autologous bone marrow derived mesenchymal stem cells administered retrobulbar, subtenon, intravitreal and intravenous. At 8 month follow up, the patient’s visual acuity in the right eye improved from 20/80 to 20/60 and improved in the left eye from 20/50 to 20/30. Additionally, the optical coherence tomography macular volume significantly increased throughout the study. Autologous bone marrow derived mesenchymal stem cells administered retrobulbar, subtenon, intravitreal and intravenous demonstrated improvement in visual acuity and macular volume in a patient with serpiginous choroidpathy when evaluated 8 months after treatment.
• Weiss JN, Levy S, Benes SC. Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow-derived stem cells in the treatment of Leber's hereditary optic neuropathy. Neural Regen Res. 2016 Oct;11(10):1685-1694. doi: 10.4103/1673-5374.193251. PMID: 27904503; PMCID: PMC5116851
  This study enrolled a total of 5 patients suffering from Leber’s hereditary optic neuropathy. Patients were treated with autologous bone marrow derived stem cells administered in a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal and intravenous depending on the nature of disease and degree of vision loss. Patient 2 demonstrated a baseline ETDRS of 0 pretreatment in both eyes. At 16 months, this increased to 6 in the right eye and 7 in the left eye. Visual fields continued to significantly improve at 16 months post treatment. Patient 3 had no light perception in the right eye at baseline and could only see hand motion in the left eye. The right eye remained unchanged but the visual acuity of the left eye improved to 20/200 at 9 months and maintained this improvement at 1 year follow up. Patient 4 could only count fingers at 6 feet before treatment. 7 months post-treatment, visual acuity improved to 20/100 in the right eye and 20/350 in the left eye. ETDRS at baseline for this patient was 18 letters at 1 meter in the right eye and 2 letters at 1 meter in the left eye. This improved to 42 letters in the right eye and 28 letters in the left eye at 7 month follow up. Patient 5 presented with a visual acuity of 6/270 in the right eye and 6/270 in the left eye. 8 months after treatment, this improved to 6/240 in the right eye and 6/210 in the left eye. Autologous bone marrow derived stem cells administered in a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal and intravenous demonstrated significant improvement in visual acuity for up to 16 months in patients with Leber’s hereditary optic neuropathy.
• Weiss JN, Levy S, Benes SC. Stem Cell Ophthalmology Treatment Study: bone marrow derived stem cells in the treatment of non-arteritic ischemic optic neuropathy (NAION). Stem Cell Investig. 2017 Nov 23;4:94. doi: 10.21037/sci.2017.11.05. PMID: 29270420; PMCID: PMC5723737.
  10 patients with bilateral vision loss secondary to non-arteritic ischemic optic neuropathy were enrolled in this study. Patients were treated with bone marrow derived stem cells administered either retrobulbar, subtenons and intravenous or following vitrectomy intra-optic nerve, subtenons and intravenous. After treatment, 80% of patients experienced improvement in Snellen binocular vision, while the other 20% remained stable. 73.6% of treated eyes demonstrated improved vision. There was an average increase of 3.53 Snellen lines per eye and an average of 22.74% improvement in LogMAR acuity per eye. It was noted that most improvements manifested within 6 months of treatment. Autologous bone marrow derived stem cells administered retrobulbar, subtenons and IV or following vitrectomy intra-optic nerve, subtenons and IV for patients with non-arteritic ischemic optic neuropathy demonstrated significant improvement in visual acuity.
• Weiss JN, Levy S. Stem Cell Ophthalmology Treatment Study: bone marrow derived stem cells in the treatment of Retinitis Pigmentosa. Stem Cell Investig. 2018;5:18. Published 2018 Jun 6. doi:10.21037/sci.2018.04.02
  17 patients with bilateral vision loss secondary to retinitis pigmentosa were enrolled in this study. Patients were treated with autologous bone marrow derived stem cells administered retrobulbar, subtenons and IV +/- intravitreal. 45.5% of treated eyes demonstrated improvement in Snellen acuity, with an average of 7.9 lines improvement. Overall visual acuity improved an average of 40.9%. LogMAR evaluation showed an average improvement of 31% improvement from baseline. Autologous bone marrow derived stem cells administered retrobulbar, subtenons and IV +/- intravitreal for patients with retinitis pigmentosa demonstrated statistically significant improvement in visual acuity when compared to baseline.
• Weiss JN, Levy S. Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow derived stem cells in the treatment of Usher syndrome. Stem Cell Investig. 2019;6:31. Published 2019 Sep 9. doi:10.21037/sci.2019.08.07
  5 patients diagnosed with usher syndrome were enrolled in this study. Patients were treated with autologous bone marrow derived stem cells administered retrobulbar, subtenons, intravitreal and intravenous. After treatment, 80% of eyes showed improvement in visual acuity, with an average overall improvement of 28.3% when assessed with LogMAR. Autologous bone marrow derived stem cells administered retrobulbar, subtenons, intravitreal and intravenous in patients with Usher syndrome resulted in improved visual acuity post-operatively.
• Weiss JN, Levy S, Malkin A. Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a preliminary report. Neural Regen Res. 2015 Jun;10(6):982-8. doi: 10.4103/1673-5374.158365. PMID: 26199618; PMCID: PMC4498363.
  This study enrolled a single 27 year old female. The patient suffered from idiopathic bilateral optic neuritis, which resulted in bilateral optic neuropathy. The patient was treated with autologous bone marrow derived stem cells administered retrobulbar, subtenon and intravitreal for the right eye and vitrectomy with direct intra-optic nerve injection for the left eye, followed by intravenous infusion. Pretreatment her visual acuity was 5/200 in the right eye and 1/200 in the left eye. 6 months after treatment her visual acuity improved to 20/100 in the right eye and 20/40 in the left eye. One year after treatment her vision in the right eye remained 20/80 and her left eye was 20/40.

Fractures

• Desai P, Hasan SM, Zambrana L, Hegde V, Saleh A, Cohn MR, Lane JM. Bone Mesenchymal Stem Cellswith Growth Factors Successfully Treat Nonunions and Delayed Unions. HSS J. 2015 Jul;11(2):104-11.doi: 10.1007/s11420-015-9432-1. Epub 2015 Mar 25. PMID: 26140028; PMCID: PMC4481261.

49 patients with tibial nonunion received bone marrow aspirate concentrates injection with demineralized bone matrix and/or recombinant human bone morphogenic protein-2. Patients were observed until they reached radiographic healing (bridging of ¾ cortices on AP and lateral films) or underwent another procedure. The use of recombinant human bone morphogenic protein-2 was associated with lower healing rate as compared to demineralized bone matrix. Early intervention was associated with higher union rates.

• Centeno CJ, Schultz JR, Cheever M, Freeman M, Robinson B, et al. (2011) A Case Series of Percutaneous Treatment of Non-Union Fractures with Autologous, Culture Expanded, Bone MarrowDerived, Mesenchymal Stem Cells and Platelet Lysate. J Bioengineer & Biomedical Sci S2:007.doi:10.4172/2155-9538.S2-007

6 patients with chronic fracture non-unions received autologous mesenchymal stem cells injected percutaneously. This method of treatment may be an alternative for non-operative treatment recalcitrant non-union fractures.

• Liebergall, M., Schroeder, J., Mosheiff, R., Gazit, Z., Yoram, Z., Rasooly, L., Daskal, A., Khoury, A., Weil, Y., & Beyth, S. (2013). Stem cell-based therapy for prevention of delayed fracture union: a randomized and prospective preliminary study. Molecular therapy : the journal of the American Society of Gene Therapy, 21(8), 1631–1638. https://doi.org/10.1038/mt.2013.109

24 patients with distal tibial fractures were randomized into a control group and a group receiving MSCs and PRP mixed with demineralized bone matrix. The median time to fracture union was 1.5 months in the intervention group and 3 months in the control group.

• Castillo-Cardiel, G., López-Echaury, A. C., Saucedo-Ortiz, J. A., Fuentes-Orozco, C., Michel-Espinoza, L. R., Irusteta-Jiménez, L., Salazar-Parra, M., & González-Ojeda, A. (2017). Bone regeneration in mandibular fractures after the application of autologous mesenchymal stem cells, a randomized clinical trial. Dental traumatology : official publication of International Association for Dental Traumatology, 33(1), 38–44. https://doi.org/10.1111/edt.12303

20 patients with mandibular angle fractures were divided into 2 groups: study group fracture reduction plus autologous mesenchymal stem cells and study group fracture reduction alone. Similar ossification rates were observed for each group after 4 weeks but after 12 weeks, the MSC group had a higher ossification rate.

Heart Failure

• Kim SH, Cho JH, Lee YH, Lee JH, Kim SS, Kim MY, Lee MG, Kang WY, Lee KS, Ahn YK, Jeong MH, Kim HS. Improvement in Left Ventricular Function with Intracoronary Mesenchymal Stem Cell Therapy in a Patient with Anterior Wall ST-Segment Elevation Myocardial Infarction. Cardiovasc Drugs Ther. 2018 Aug;32(4):329-338. doi: 10.1007/s10557-018-6804-z. PMID: 29956042; PMCID: PMC6133167.

26 patients who underwent PCI for acute anterior wall ST segment elevation myocardial infarction were included in this study. 12 patients were assigned to the control group and 14 patients received 7.2x10^7 cultured autologous bone marrow derived mesenchymal stem cells administered through a perfusion catheter 1 month after PCI. 4 months after treatment, the experimental group had an increase in LVEF of 8.8% and the control group had an increase of 4.8%. At 12 months after treatment, the experimental group had an increase in LVEF of 9.9% while the control group had an increase of 6.5%. Cell therapy was not related to an increase in any adverse events. Administration of cultured autologous bone marrow derived mesenchymal stem cells via a perfusion catheter increased LVEF at 4 and 12 months compared to control, without any cell related serious adverse events.

• Mathiasen AB, Qayyum AA, Jørgensen E, Helqvist S, Kofoed KF, Haack-Sørensen M, Ekblond A, Kastrup J. Bone marrow-derived mesenchymal stromal cell treatment in patients with ischaemic heart failure: final 4-year follow-up of the MSC-HF trial. Eur J Heart Fail. 2020 May;22(5):884-892. doi: 10.1002/ejhf.1700. Epub 2019 Dec 21. PMID: 31863561.

60 patients with ischemic heart failure were enrolled in this study. 20 patients were used as controls and 40 patients received intramyocardial injections of cultured autologous bone marrow derived mesenchymal stem cells. Patients were treated with an average of 77.5x10^6 MSCs. After 12 months, LVESV was significantly reduced in the MSC group and not in the placebo group, with a difference between groups of 17.0mL. There was also a significant difference between groups of 6.2% in LVEF, 16.1mL of stroke volume and significant difference in myocardial mass. A significant dose response curve was observed, with greater amount of stem cells providing greater efficacy. Significant improvements in amount of scar tissue as well as quality of life indexes were seen in the experimental group, but not in the control group. Intramyocardial injection of autologous bone marrow derived mesenchymal stem cells resulted in significant improvement in LVESV, LVEF, scar tissue and quality of life compared to placebo at 12 months.

• Bartolucci J, Verdugo FJ, González PL, Larrea RE, Abarzua E, Goset C, Rojo P, Palma I, Lamich R, Pedreros PA, Valdivia G, Lopez VM, Nazzal C, Alcayaga-Miranda F, Cuenca J, Brobeck MJ, Patel AN, Figueroa FE, Khoury M. Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]). Circ Res. 2017 Oct 27;121(10):1192-1204. doi: 10.1161/CIRCRESAHA.117.310712. Epub 2017 Sep 26. PMID: 28974553; PMCID: PMC6372053.

Patients suffering from heart failure with reduced ejection fraction were enrolled in this study. 15 patients were used as control and the other 15 patients received 1x10^6/kg cultured allogeneic umbilical cord derived mesenchymal stem cells administered intravenously. No treatment related adverse events were observed. Echocardiograph after 12 months showed significant differences in the improvements of LVEF with a 7.07 increase in the experimental group and a 1.85 in the control group. Additionally, patients in the experimental group showed improvements in the NYHA class and MLHF questionnaire, whereas the control group did not. Intravenous administration of cultured allogeneic umbilical cord derived MSCs resulted in significant improvement in LVEF, NYHA class and MLHF questionnaire at 12 months compared to the placebo group.

• Butler J, Epstein SE, Greene SJ, Quyyumi AA, Sikora S, Kim RJ, Anderson AS, Wilcox JE, Tankovich NI, Lipinski MJ, Ko YA, Margulies KB, Cole RT, Skopicki HA, Gheorghiade M. Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial. Circ Res. 2017 Jan 20;120(2):332-340. doi: 10.1161/CIRCRESAHA.116.309717. Epub 2016 Nov 16. PMID: 27856497.

22 patients with nonischemic cardiomyopathy were enrolled in this study. 10 patients initially received intravenous administration of 1.5x10^6/kg cultured allogeneic bone marrow derived mesenchymal stem cells and the other 12 received placebo. After 90 days, the two cohorts switched. There were no treatment related serious adverse events. Compared with placebo, MSC therapy increased 6 minute walk distance, Kansas City Cardiomyopathy clinical summary and functional status score. No significant differences were noted in LVEF or ventricular volume. Intravenous administration of cultured allogeneic bone marrow derived mesenchymal stem cells resulted in improved 6 minute walk test, Kansas city cardiomyopathy clinical summary and functional status score. No treatment related serious adverse events.

Idiopathic Pulmonary Fibrosis

• First‐in‐human high‐cumulative‐dose stem cell therapy in idiopathic pulmonary fibrosis with rapid lung function decline
  Alexander Averyanov
  Dr. Averyanov’s phase I/IIa clinical trial enrolled 20 patients, 10 of which received treatment and the other 10 received placebo. The treatment group received two IV doses of cultured 2x10^8 allogeneic bone marrow MSCs every 3 months for a total of 12 months.  At the end of the 12 month study period, the experimental group had a 3.7% FVC increase from baseline while the placebo group had a 9.5% decrease from baseline. The experimental group had an increase of 24.2% in the 6MWTD while the placebo group had a 9.8% decrease. The experimental group had a 5.1% decrease in DLCO while the placebo group had a 12.9% decrease, demonstrating significant improvement in all 3 parameters.  Repeat allogeneic bone marrow mesenchymal stem cells administered intravenously demonstrated significantly improved FVC, DLCO and 6MWTD at 12 months compared to the control group.
• Intravenous stem cell dose and changes in quantitative lung fibrosis and DLCO in the AETHER trial: a pilot study
  J E Fishman
  Dr. Fishman’s phase 1 clinical trial treated 6 patients with mild to moderate IPF. These 6 patients were separated into two cohorts. Cohort 1 received single infusion of 2x10^7 allogeneic  bone marrow derived mesenchymal stem cells intravenously and Cohort 2 received single infusion of 1x10^8 bone marrow derived mesenchymal stem cells, intravenously. From baseline to 48 weeks cohort 2 demonstrated statistically significant better results than cohort 1 in quantitative lung fibrosis (+1.13% vs +4.00%), forced vital capacity (-3.84L vs -5.85L), total lung capacity (+9.95L vs –1.24) and Diffusing Capacity of Lung for Carbon Monoxide (-2 vs -17). This study demonstrated a dose dependent improvement for allogeneic bone marrow derived mesenchymal stem cells administered intravenously in quantitative lung fibrosis, FVC, TLC and DLCO, with the higher dose demonstrating significant improvement compared to the low dosage group 2 years after treatment.

Click here for the clinical trial for Idiopathic Pulmonary Fibrosis

Inflammatory Bowel Disease

Crohn's Disease

• Zhang J, Lv S, Liu X, Song B, Shi L. Umbilical Cord Mesenchymal Stem Cell Treatment for Crohn's Disease: A Randomized Controlled Clinical Trial. Gut Liver. 2018 Jan 15;12(1):73-78. doi: 10.5009/gnl17035. PMID: 28873511; PMCID: PMC5753687.
  Dr. Zhang’s clinical trial treated 41 patients with 4 intravenous infusions one per week of 1 million umbilical cord mesenchymal stem cells per kilogram. After 1 year of follow up, CDAI scores improved from 281.5 to 219.0. Corticosteroid use also improved from 13.6 mg/day to 9.4.  HBI improved from 12.7 to 9.3 Intravenous infusion of umbilical cord mesenchymal stem cells demonstrated efficacy in improving symptoms associated with CD and decreased reliance on corticosteroids.
• Forbes GM, Sturm MJ, Leong RW, Sparrow MP, Segarajasingam D, Cummins AG, Phillips M, Herrmann RP. A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn's disease refractory to biologic therapy. Clin Gastroenterol Hepatol. 2014 Jan;12(1):64-71. doi: 10.1016/j.cgh.2013.06.021. Epub 2013 Jul 19. PMID: 23872668.
  Dr. Forbes’ clinical trial treated 15 patients, each with 4 IV infusions of 2 million cultured allogenic bone marrow mesenchymal stem cells per kilogram once per week. At day 42, the average CDAI score had improved from 370 to 203. 12 patients showed a clinically significant response, and 8 had clinical remission. Cultured allogeneic bone marrow derived mesenchymal stem cells demonstrated efficacy in improving symptoms associated with CD and inducing remission.  

Ulcerative Colitis

• Hu J, Zhao G, Zhang L, Qiao C, Di A, Gao H, Xu H. Safety and therapeutic effect of mesenchymal stem cell infusion on moderate to severe ulcerative colitis. Exp Ther Med. 2016 Nov;12(5):2983-2989. doi: 10.3892/etm.2016.3724. Epub 2016 Sep 20. PMID: 27882104; PMCID: PMC5103734.
  Dr. Hu’s clinical trial examined 36 controls and treated 34 patients with two injections of umbilical cord mesenchymal stem cells – one intravenous of dose 0.5M/kg intravenous and one of dose 15M cells into the superior mesenteric artery by cauterization 7 days apart. 30 patients showed a positive response. The mayo scores significantly improved in 85.3% in the treatment group, and only 15.7% in the control. The IBDQ scores of the treatment group improved from 128.6 to 181.9 at 3 months. Intravenous, in conjunction with intra-arterial administration of umbilical cord mesenchymal stem cells demonstrated efficacy in improving symptoms associated with ulcerative colitis. 
• https://www.omicsonline.org/proceedings/umbilical-cord-blood-stem-cell-transplantation-for-the-treatment-of-ulcerative-colitis-29465.html
  Dr. Xu’s clinical trial had 66 controls and treated 81 patients with umbilical cord blood mesenchymal stem cells into the inferior mesenteric artery. Clinical symptoms disappeared at week 4 and did not relapse in the 24 weeks follow up. Intra-arterial administration of umbilical cord mesenchymal stem cells demonstrated efficacy in decreasing symptoms associated with ulcerative colitis and preventing symptom relapse.

Click here for the clinical trial for Inflammatory Bowel Disease

Interstitial Cystitis

• Lander EB, Berman MH, See JR. Personal cell therapy for interstitial cystitis with autologous stromal vascular fraction stem cells. Ther Adv Urol. 2019 Aug 17;11:1756287219868590. doi: 10.1177/1756287219868590. PMID: 31452686; PMCID: PMC6698997.

109 patients with interstitial cystitis were included in this study. Patients underwent lipoaspirate and received SVF administered intravenously and injected regionally into the pelvic floor muscles. Overall, average pain scores from baseline decreased from 5.14 to 3.67 at 12 months. The Pelvic pain and urgency/frequency patient symptom scale also improved from 21.42 to 14.2 at 12 months. Intravenous and regional administration of SVF resulted in significantly decreased pain and improved symptom rating scale when reassessed 12 months after treatment.

• Wiafe B, Adesida AB, Churchill T, Kadam R, Carleton J, Metcalfe PD. Mesenchymal stem cell therapy inhibited inflammatory and profibrotic pathways induced by partial bladder outlet obstruction and prevented high-pressure urine storage. J Pediatr Urol. 2019 May;15(3):254.e1-254.e10. doi: 10.1016/j.jpurol.2019.03.003. Epub 2019 Mar 12. PMID: 30967358.

20 rats included in this study and had outlet obstruction surgically induced and then treated with intravenous injection of bone marrow derived mesenchymal stem cells. By two weeks after treatment there was significant reduction in TNF-alpha and increase in IL-10 and VEGF. By 4 weeks after treatment there was significant downregulation in profibrotic genes. End filling pressure, hypertrophy and fibrosis were all significantly reduced after 4 weeks. Intravenous injection of bone marrow derived mesenchymal stem cells resulted in anti-inflammatory cytokine preference and decreased filling pressure, bladder hypertrophy and bladder fibrosis after 4 weeks.

• Chung JW, Chun SY, Lee EH, Ha YS, Lee JN, Song PH, Yoo ES, Kwon TG, Chung SK, Kim BS. Verification of mesenchymal stem cell injection therapy for interstitial cystitis in a rat model. PLoS One. 2019 Dec 12;14(12):e0226390. doi: 10.1371/journal.pone.0226390. PMID: 31830131; PMCID: PMC6907861.

Rats with induced interstitial cystitis included in this study.  Rats were treated with either urine derived MSCs, adipose derived MSCs, bone marrow derived and amniotic fluid-derived MSCs. Additionally, all groups had participants with routes either direct into the bladder mucosa, into the tail vein, or transurethral installation. Reassessment was performed 10 days after treatment. Intercontraction interval was significantly increased and inflammatory reactions/fibrotic changes were decreased in all of the stem cell injected groups compared to the control group. PCR revealed significantly decreased fibrotic gene expression in the urine derived stem cell group compared to the others. The groups that received stem cells administered directly into the bladder submucosa showed significantly longer intercontraction interval, better morphological regeneration and inhibition of bladder inflammatory reaction compared with the other groups. Administration of stem cells increased intercontraction interval and decreased inflammatory changes of rats with induced interstitial cystitis. Urine derived stem cells showed the greatest reduction in fibrotic gene expression. Direct injection into the bladder submucosa showed greater clinical efficacy than alternative routes of administration

Kidney Disease

• Belingheri M, Lazzari L, Parazzi V, Groppali E, Biagi E, Gaipa G, Giordano R, Rastaldi MP, Croci D, Biondi A, Rebulla P, Edefonti A, Ghio L. Allogeneic mesenchymal stem cell infusion for the stabilization of focal segmental glomerulosclerosis. Biologicals. 2013 Nov;41(6):439-45. doi: 10.1016/j.biologicals.2013.09.004. Epub 2013 Oct 14. PMID: 24135082.  
  This is a single patient case report regarding a 13 year old with FSGS. After diagnosis he received a renal transplant with subsequent recurrence of FSGS after transplant. He developed worsening proteinuria and needed weekly plasmapharesis to achieve partial control of the proteinuria (uPr/uCr <5). 7, 10 and 14 months after transplant patient was treated with cultured allogeneic bone marrow derived mesenchymal stem cells administered intravenously. 22 months after the third treatment the patient maintained normal renal function. Serum creatinine was .96 and GFR was 94. The uPr/uCr ratio maintained under 5 without additional plasmapharesis. Intravenous infusion of cultured allogeneic bone marrow derived mesenchymal stem cells demonstrated the ability to stabilize the effects of FSGS. Proteinuria, which required plasmapharesis weekly prior to transplantation, no longer required plasmapharesis for 22 weeks after treatment.  
• Nassar W, El-Ansary M, Sabry D, Mostafa MA, Fayad T, Kotb E, Temraz M, Saad AN, Essa W, Adel H. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater Res. 2016 Aug 5;20:21. doi: 10.1186/s40824-016-0068-0. Erratum in: Biomater Res. 2017 Apr 6;21:3. PMID: 27499886; PMCID: PMC4974791.  
  40 patients with CKD included in this study. 20 patients were used as controls. 20 Patients received mesenchymal stromal cell derived extracellular vesicles administered intravenously and intra-arterial. The experimental group demonstrated significant improvement in eGFR and serum creatinine at 12 weeks compared to baseline. At one year, when comparing the treatment group to the control group, the difference in improvement in eGFR was 11, which was statistically significant. The difference in improvement for Blood urea, creatinine and urinary albumin creatinine ratio were 78, 2.1 and 266, respectively. The improvement from baseline compared between the two groups was significant for all these parameters. Intravenous and intra-arterial infusion of mesenchymal stromal cell derived extracellular vesicles demonstrated significant improvement at 1 year in eGFR, Blood urea, serum creatinine and urinary albumin creatinine ratio when compared to the control group.
• Rahyussalim AJ, Saleh I, Kurniawati T, Lutfi APWY. Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report. J Med Case Rep. 2017 Nov 30;11(1):334. doi: 10.1186/s13256-017-1489-7. PMID: 29187247; PMCID: PMC5707902.
  Single patient who was diagnosed with chronic kidney disease and spinal cord entrapment, likely secondary to diabetes mellitus. Prior to treatment, patient had not produced urine for 2 years and was diagnosed with ESRD. Patient underwent treatment with human umbilical cord derived mesenchymal stem cells administered intrathecally and intravenously. The patient received six cycles of this treatment, each 3 months apart and consisting of 16 million cells. After the first treatment, patient urinated for the first time in 2 years. Her baseline creatinine was 11, which decreased to 2 after the second treatment. Patient with ESRD received human umbilical cord mesenchymal stem cells delivered intravenously and intrathecally. After first treatment, she was able to urinate for the first time in 2 years. After second treatment her creatinine decreased to 2, down from 11 at baseline.
• Wang D, Li J, Zhang Y, Zhang M, Chen J, Li X, Hu X, Jiang S, Shi S, Sun L. Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study. Arthritis Res Ther. 2014 Mar 25;16(2):R79. doi: 10.1186/ar4520. PMID: 24661633; PMCID: PMC4060570.
  40 patients included in this study and treated with cultured allogeneic umbilical cord mesenchymal stem cells administered intravenously. Patients received two infusions, seven days apart. SLEDAI and BILAG both demonstrated significant improvement 1 month after treatment and demonstrated continued improvement when reassessed at 12 months after treatment. Renal function, as assessed by 24-hour proteinuria demonstrated significant improvement at 9 and 12 months when compared to baseline. Intravenous infusion of cultured umbilical cord mesenchymal stem cells demonstrated significant improvement in disease activity indexes and renal function at 12 months when compared to baseline.
• Wang D, Zhang H, Liang J, Li X, Feng X, Wang H, Hua B, Liu B, Lu L, Gilkeson GS, Silver RM, Chen W, Shi S, Sun L. Allogeneic mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus: 4 years of experience. Cell Transplant. 2013;22(12):2267-77. doi: 10.3727/096368911X582769c. PMID: 24388428.
  87 patients were included in this study. Patients were either treated with cultured allogeneic bone marrow mesenchymal cells from healthy relative or cultured allogeneic umbilical cord mesenchymal stem cells. Mesenchymal stem cells were administered intravenously. Hemoglobin and platelet count showed significant improvement 12 months after treatment. SLEDAI showed significant improvement 1 month after treatment and this was sustained until 3 years after treatment. Renal function, as assessed by 24 hour proteinuria, serum urea nitrogen and serum creatinine all showed significant improvement 12 months after treatment. Intravenous infusion of cultured mesenchymal stem cells showed significant improvement in improving cytopenia, improving symptoms associated with SLE and improving renal function was reassessed 12 months after treatment.
• Gu F, Wang D, Zhang H, Feng X, Gilkeson GS, Shi S, Sun L. Allogeneic mesenchymal stem cell transplantation for lupus nephritis patients refractory to conventional therapy. Clin Rheumatol. 2014 Nov;33(11):1611-9. doi: 10.1007/s10067-014-2754-4. Epub 2014 Aug 14. PMID: 25119864.
  81 patients included in this study and either received cultured allogeneic umbilical cord mesenchymal stem cells or cultured allogeneic bone marrow derived mesenchymal stem cells. Cells were administered intravenously. Renal function, as measured by BILAG scores significantly improved at 12 months compared to baseline. Additionally, GFR also improved significantly at 12 months compared to baseline. Total disease activity, as evaluated by SLEDAI improved significantly at 12 months when compared to baseline. Intravenous infusion of cultured allogeneic mesenchymal stem cells demonstrated significant improvement in renal function, as assessed by BILAG and GFR, and total disease activity, as assessed by SLEDAI, at 12 months when compared to baseline.
• Liang J, Zhang H, Hua B, Wang H, Lu L, Shi S, Hou Y, Zeng X, Gilkeson GS, Sun L. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis. 2010 Aug;69(8):1423-9. doi: 10.1136/ard.2009.123463. Erratum in: Ann Rheum Dis. 2011 Jan;70(1):237. PMID: 20650877.
  15 patients included in this study. All treated with cultured allogeneic bone marrow derived mesenchymal stem cells administered intravenously. Baseline SLEDAI was 12.1 at baseline and improved significantly to 3.2 at 12 month follow up. Proteinuria at baseline was 2505, which significantly improved to 858 at 12 month follow up. Additionally, individual patients had specific improvements related to their disease status. 11 patients originally had fatigure/ weight loss/ low grade fever and 8 of these patients were free of these manifestations 3 months after treatment. 8 patients had rashes prior to treatment. 4 of these patients had complete resolution and the other 4 had partial resolution by 3 month follow up. Intravenous treatment of cultured allogeneic bone marrow derived mesenchymal stem cells showed significant improvement in SLEDAI and proteinuria when reassessed 12 months after treatment. Additional manifestations including fatigue, weight loss and rashes showed improvement at 3 months for people suffering these symptoms.

Click here for the clinical trial for Kidney Disease

Leg and foot ulcer

• Lu D, Chen B, Liang Z, Deng W, Jiang Y, Li S, Xu J, Wu Q, Zhang Z, Xie B, Chen S. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract. 2011 Apr;92(1):26-36. doi: 10.1016/j.diabres.2010.12.010. Epub 2011 Jan 8. PMID: 21216483.
  41 diabetics with chronic limb ischemia were enrolled in this study. Patients received either intramuscular injection of bone marrow mesenchymal stem cells or bone marrow mononuclear cells. Ulcer healing rate was significantly higher in the mesenchymal stem cell group after 6 weeks than the bone marrow mononuclear cells. After 6 months, the stem cell group showed significant improvement compared to the mononuclear cell group in painless walking time, ABI, TcO2 and magnetic resonance angiography. Intramuscular injection of bone marrow mesenchymal stem cells showed higher efficacy than bone marrow mononuclear cells in would healing shortly after procedure. After 24 weeks, the stem cell group showed significant improvement compared to mononuclear cells in assessments of limb perfusion.
• Carstens MH, Gómez A, Cortés R, Turner E, Pérez C, Ocon M, Correa D. Non-reconstructable peripheral vascular disease of the lower extremity in ten patients treated with adipose-derived stromal vascular fraction cells. Stem Cell Res. 2017 Jan;18:14-21. doi: 10.1016/j.scr.2016.12.001. Epub 2016 Dec 8. PMID: 27984756.
  10 patients with peripheral vascular disease secondary to arteriosclerosis and/or DM were treated with SVF. Injections were intramuscular into gastrocnemius and around the level of the lesion (if lesion present). Four of five patients with ulcers demonstrated complete closure in eight to nine months with no recurrence after 18 months. All patients demonstrated clinical improvement in decreased pain, claudication and improvements in ABI at 4 month follow up. Intramuscular and intra-lesional injections of SVF resulted in improvement in pain, claudication and improvements in ABI after 4 months. Patients with chronic wounds had complete close within 9 months and no patient had ulcer recurrence in 18 months. 
• Lasala GP, Silva JA, Minguell JJ. Therapeutic angiogenesis in patients with severe limb ischemia by transplantation of a combination stem cell product. J Thorac Cardiovasc Surg. 2012 Aug;144(2):377-82. doi: 10.1016/j.jtcvs.2011.08.053. Epub 2011 Nov 12. PMID: 22079876. (full text available)
  26 patients were enrolled in this study. Patients received combined autologous bone marrow mononuclear cells and bone marrow mesenchymal stem cells injected intramuscularly into the gastrocnemius of the more severe leg. Less severe leg was used as a control. ABI showed significant improvement after 1 month in the experimental leg and this was sustained at last follow up at 4 months. There was no improvement in the less severe leg used as control. All patients demonstrated increase in pain free walking as measured by walking time. Results were significant as early as 2 weeks after treatment and remained significant for 4 months. This improvement was directly correlated with improved pain severity and relief. Intramuscular treatment with combination of autologous bone marrow mononuclear cells and bone marrow derived mesenchymal stem cells demonstrated significant improvement in ABI, walking and pain severity as early as 2 weeks after treatment and sustained for duration of follow up at 4 months after treatment. 
• Qin HL, Zhu XH, Zhang B, Zhou L, Wang WY. Clinical Evaluation of Human Umbilical Cord Mesenchymal Stem Cell Transplantation After Angioplasty for Diabetic Foot. Exp Clin Endocrinol Diabetes. 2016 Sep;124(8):497-503. doi: 10.1055/s-0042-103684. Epub 2016 May 24. PMID: 27219884.
  72 limbs were included in this study. All limbs underwent angioplasty and after, half the limbs were placed into the control group (no further management) and half were placed into the experimental group. The experimental group received human umbilical cord mesenchymal stem cells administered via endovascular infusion and injection around the foot ulcer. 3 months after treatment the experimental group experienced significantly greater improvement in skin temperature, ABI, transcutaneous oxygen tension and claudication distance. Additionally, the experimental group had significant increase in neovessels and ulcer healings. Umbilical stem cells administered endovascularly and around foot ulcer after angioplasty showed significant improvement at 3 months in ulcer healing, skin temperature, ABI, transcutaneous oxygen tension and claudication disrance.
• Lu D, Jiang Y, Deng W, Zhang Y, Liang Z, Wu Q, Jiang X, Zhang L, Gao F, Cao Y, Chen B, Xue Y. Long-Term Outcomes of BMMSC Compared with BMMNC for Treatment of Critical Limb Ischemia and Foot Ulcer in Patients with Diabetes. Cell Transplant. 2019 May;28(5):645-652. doi: 10.1177/0963689719835177. Epub 2019 Mar 27. PMID: 30917698; PMCID: PMC7103602.
  41 patients included in the study. Half received bone marrow mesenchymal stem cells and half received bone marrow mononuclear cells in one leg. Other leg was used as control in each patient. Treatment was administered intramuscularly with a small amount injected into basilar part of each foot ulcer and surrounding subcutaneous tissue. At 6 months there was significant reduction in both treatment groups in amputations, this improvement was not sustained at 3 year follow up. Ulcer rate recurrence, angiographic score, pain free walking, rest pain, ABI and TcO2 improved in both experimental groups between 3-9 months but none of these results were sustained at further follow up. Intramuscular and intralesional injection of bone marrow derived mononuclear cells and mesenchymal stem cells showed improvement in amputation rates, blood flow and subjective efficacy outcomes between 3-9 months. None were sustained beyond this point. 
• Dubsky M, Jirkovska A, Bem R, Fejfarova V, Pagacova L, Sixta B, Varga M, Langkramer S, Sykova E, Jude EB. Both autologous bone marrow mononuclear cell and peripheral blood progenitor cell therapies similarly improve ischaemia in patients with diabetic foot in comparison with control treatment. Diabetes Metab Res Rev. 2013 Jul;29(5):369-76. doi: 10.1002/dmrr.2399. PMID: 23390092.  
  50 patients with diabetic foot ulcers included in this study. 17 patients were treated with autologous bone marrow mononuclear cells, 11 patients were treated with autologous peripheral blood cells and 22 patients were used as control. Treatment was injected into the patients’ calves along with the dorsal and plantar muscles of the affected lower limb. 1/28 patients in the experimental group died and another three underwent major amputation. 2/22 patients in the control group died and another 10 underwent amputation. Rate of major amputation was significantly lower in the experimental group. The number of healed ulcers was also significantly higher in the experimental group compared to control ( 14/25 compared to 3/18). TcPO2 improved in the experimental group after 4 weeks and this was sustained at 6 months. There was no difference between BMMNC and PBPC. TcPO2 worsened in the control group after 6 months. Intramuscular injection of BMMNC and PBPC demonstrated significant improvement compared to control when evaluating rates of amputation, healing of ulcers and tissue oxygenation when evaluated 6 months after treatment. 
• Li M, Zhou H, Jin X, Wang M, Zhang S, Xu L. Autologous bone marrow mononuclear cells transplant in patients with critical leg ischemia: preliminary clinical results. Exp Clin Transplant. 2013 Oct;11(5):435-9. doi: 10.6002/ect.2012.0129. Epub 2013 Mar 11. PMID: 23477421.
  58 patients with critical limb ischemia included in study. Half control and half experimental. Experimental group treated with autologous bone marrow mononuclear cells administered intramuscularly into the muscles of the ischemic area. At 6 month follow up, the experimental group demonstrated significant hemodynamic improvement, improvement in skin ulcer and decrease in pain. Intramuscular injection of bone marrow mononuclear cells demonstrated significant improvement in hemodynamic improvement, skin ulcer healing and decrease in pain compared to placebo at 6 months.

Lupus

• Li X, Wang D, Liang J, Zhang H, Sun L. Mesenchymal SCT ameliorates refractory cytopenia in patients with systemic lupus erythematosus. Bone Marrow Transplant. 2013 Apr;48(4):544-50. doi: 10.1038/bmt.2012.184. Epub 2012 Oct 15. PMID: 23064040.
  35 patients enrolled in this study. 8 patients had healthy relatives to donate cultured allogeneic bone marrow derived mesenchymal stem cells. The other 27 patients did not and received allogeneic cultured umbilical cord derived mesenchymal stem cells. Pretreatment SLEDAI was around 12.3, which decreased to 4.2 after 1 year. Leukocyte count increased from 2.52 x10^9 at baseline to 3.83x10^9 at 1 year for patients who started with pretreatment leukopenia. For patients with pretreatment thrombocytopenia, with an average platelet count average of 37.07 x10^9, 12 month reevaluation demonstrated improvement to an average of 98.5x10^9. Baseline hemoglobin was 74g/L, which increased to an average of 93g/L at 12 months. Cultured allogeneic umbilical cord mesenchymal stem cells and cultured allogeneic bone marrow derived mesenchymal stem cells demonstrated significant improvement in treating disease symptoms along with the pancytopenia associated with SLE at 12 months.
• Wang D, Li J, Zhang Y, Zhang M, Chen J, Li X, Hu X, Jiang S, Shi S, Sun L. Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study. Arthritis Res Ther. 2014 Mar 25;16(2):R79. doi: 10.1186/ar4520. PMID: 24661633; PMCID: PMC4060570.
  40 patients included in this study and treated with cultured allogeneic umbilical cord mesenchymal stem cells administered intravenously. Patients received two infusions, seven days apart. SLEDAI and BILAG both demonstrated significant improvement 1 month after treatment and demonstrated continued improvement when reassessed at 12 months after treatment. Renal function, as assessed by 24-hour proteinuria demonstrated significant improvement at 9 and 12 months when compared to baseline. Intravenous infusion of cultured umbilical cord mesenchymal stem cells demonstrated significant improvement in disease activity indexes and renal function at 12 months when compared to baseline.
• Wang D, Zhang H, Liang J, Li X, Feng X, Wang H, Hua B, Liu B, Lu L, Gilkeson GS, Silver RM, Chen W, Shi S, Sun L. Allogeneic mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus: 4 years of experience. Cell Transplant. 2013;22(12):2267-77. doi: 10.3727/096368911X582769c. PMID: 24388428.
  87 patients were included in this study. Patients were either treated with cultured allogeneic bone marrow mesenchymal cells from healthy relative or cultured allogeneic umbilical cord mesenchymal stem cells. Mesenchymal stem cells were administered intravenously. Hemoglobin and platelet count showed significant improvement 12 months after treatment. SLEDAI showed significant improvement 1 month after treatment and this was sustained until 3 years after treatment. Renal function, as assessed by 24 hour proteinuria, serum urea nitrogen and serum creatinine all showed significant improvement 12 months after treatment. Intravenous infusion of cultured mesenchymal stem cells showed significant improvement in improving cytopenia, improving symptoms associated with SLE and improving renal function was reassessed 12 months after treatment.
• Gu F, Wang D, Zhang H, Feng X, Gilkeson GS, Shi S, Sun L. Allogeneic mesenchymal stem cell transplantation for lupus nephritis patients refractory to conventional therapy. Clin Rheumatol. 2014 Nov;33(11):1611-9. doi: 10.1007/s10067-014-2754-4. Epub 2014 Aug 14. PMID: 25119864.
  81 patients included in this study and either received cultured allogeneic umbilical cord mesenchymal stem cells or cultured allogeneic bone marrow derived mesenchymal stem cells. Cells were administered intravenously. Renal function, as measured by BILAG scores significantly improved at 12 months compared to baseline. Additionally, GFR also improved significantly at 12 months compared to baseline. Total disease activity, as evaluated by SLEDAI improved significantly at 12 months when compared to baseline. Intravenous infusion of cultured allogeneic mesenchymal stem cells demonstrated significant improvement in renal function, as assessed by BILAG and GFR, and total disease activity, as assessed by SLEDAI, at 12 months when compared to baseline.
• Liang J, Zhang H, Hua B, Wang H, Lu L, Shi S, Hou Y, Zeng X, Gilkeson GS, Sun L. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis. 2010 Aug;69(8):1423-9. doi: 10.1136/ard.2009.123463. Erratum in: Ann Rheum Dis. 2011 Jan;70(1):237. PMID: 20650877.
  15 patients included in this study. All treated with cultured allogeneic bone marrow derived mesenchymal stem cells administered intravenously. Baseline SLEDAI was 12.1 at baseline and improved significantly to 3.2 at 12 month follow up. Proteinuria at baseline was 2505, which significantly improved to 858 at 12 month follow up. Additionally, individual patients had specific improvements related to their disease status. 11 patients originally had fatigure/ weight loss/ low grade fever and 8 of these patients were free of these manifestations 3 months after treatment. 8 patients had rashes prior to treatment. 4 of these patients had complete resolution and the other 4 had partial resolution by 3 month follow up. Intravenous treatment of cultured allogeneic bone marrow derived mesenchymal stem cells showed significant improvement in SLEDAI and proteinuria when reassessed 12 months after treatment. Additional manifestations including fatigue, weight loss and rashes showed improvement at 3 months for people suffering these symptoms.
• Sun L, Wang D, Liang J, Zhang H, Feng X, Wang H, Hua B, Liu B, Ye S, Hu X, Xu W, Zeng X, Hou Y, Gilkeson GS, Silver RM, Lu L, Shi S. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum. 2010 Aug;62(8):2467-75. doi: 10.1002/art.27548. PMID: 20506343.
  16 patients included in this study and all treated with cultured umbilical cord mesenchymal stem cells administered intravenously. 10 of these patients were followed for 6 or more months. At 6 month follow up, SLEDAI scores decreased significantly from 19.0 before treatment to 7.3 at reassessment. Before treatment, average 24 hour proteinuria was 3237, which improved significantly to 1057 6 months after treatment. There was also significant reduction in measured serum ANA and anti-dsDNA when assessed 6 months after treatment compared to baseline. Intravenous cultured allogeneic umbilical cord mesenchymal stem cell treatment demonstrated efficacy in reducing symptoms associated with SLE, reducing proteinuria and reducing serum markers associated with disease activity when assessed 6 months after treatment.

Click here for the clinical trial for Lupus

Multiple Sclerosis

• Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, Du MQ, Luan SL, Altmann DR, Thompson AJ, Compston A, Scott MA, Miller DH, Chandran S. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol. 2012 Feb;11(2):150-6. doi: 10.1016/S1474-4422(11)70305-2. Epub 2012 Jan 10. PMID: 22236384; PMCID: PMC3279697.
  Dr. Connick’s clinical trial treated 10 patients with SPMS with autologous cultured bone marrow mesenchymal stem cells. They were administered a single dose of 1.6x10^6 cells/kg given by IV. At 6 months follow up, the researchers found evidence of improved visual acuity and optic nerve area. Prior to treatment, the EDSS had been worsening at an average rate of 0.0257 per month. In the 6 months after treatment, the EDSS was noted to improve by an average rate of 0.0012 per month. Autologous bone marrow derived mesenchymal stem cells administered IV demonstrated the ability to improve visual acuity and optic nerve area. Treatment also showed the ability to stop the decline in EDSS with a mild increase 6 months after treatment.
• Petrou P, Kassis I, Levin N, Paul F, Backner Y, Benoliel T, Oertel FC, Scheel M, Hallimi M, Yaghmour N, Hur TB, Ginzberg A, Levy Y, Abramsky O, Karussis D. Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis. Brain. 2020 Dec 1;143(12):3574-3588. doi: 10.1093/brain/awaa333. PMID: 33253391.
  Dr. Petrou’s clinical trial enrolled 48 patients. These 48 patients were split into 3 cohorts. Group 1 received 1x10^6 cultured autologous bone marrow derived mesenchymal stem cells per kilogram delivered intrathecally. Group 2 received 1x10^6 cultured autologous bone marrow derived mesenchymal stem cells per kilogram delivered intravenously. Group 3 received a placebo injection. A second injection was scheduled for 6 months after the initial injection. Patients from groups one and two either received a second injection of the same type or they received a placebo injection. The patients that initially received a placebo injection received either an intrathecal or intravenous dose.  6 months after the initial transplantation, both the IV and intrathecal groups showed statistically significant improvement in EDSS, rate of treatment failure and change in sum of functional scores compared to placebo. At this time, there was also a statistically significant difference in the change in sum of functional scores between the intrathecal and intravenous group, in favor of the intrathecal group. After 6 months, 58.6% of IT patients and 40.6% of IV patients had no evidence of disease activity compared to the 9.7% in the placebo group. Additionally, the group that received two intrathecal doses showed a statistically significant improvement after repeat treatment compared to the intravenous group, which did not show a statistically significant improvement after repeat treatment. This study demonstrated that both intrathecal and intravenous administration of cultured autologous bone marrow derived mesenchymal stem cells improved clinical symptoms significantly more than control 6 months after treatment, with intrathecal showing better outcomes than intravenous. Additionally, repeat injections was shown to be advantageous for the intrathecal group but not for the intravenous group.
• Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JW, Petrou P, Ben-Hur T, Abramsky O, Slavin S. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010 Oct;67(10):1187-94. doi: 10.1001/archneurol.2010.248. PMID: 20937945; PMCID: PMC3036569.
  Dr. Karussis’ clinical trial treated 15 patients diagnosed with MS with autologous cultured bone marrow mesenchymal stem cells. All the patients were treated with a single injection of 63.2x10^6 cells given intrathecally. 5 of the patients also received a single dose of 24.5x10^6 cells given intravenously. At the 6 month follow up, the average EDSS score improved 6.7 to 5.9 and was unchanged or improved in all patients (none worsened). This study demonstrated that cultured autologous bone marrow derived mesenchymal stem cells administered intrathecally demonstrated the ability to significantly improve EDSS scores 6 months after treatment.
• Li JF, Zhang DJ, Geng T, Chen L, Huang H, Yin HL, Zhang YZ, Lou JY, Cao B, Wang YL. The potential of human umbilical cord-derived mesenchymal stem cells as a novel cellular therapy for multiple sclerosis. Cell Transplant. 2014;23 Suppl 1:S113-22. doi: 10.3727/096368914X685005. Epub 2014 Nov 5. PMID: 25385295.
  Dr. Li’s clinical trial in China enrolled 23 patients diagnosed with MS. The experimental group (n=13) received 4x10^6 cultured human umbilical cord mesenchymal stem cells intravenously once every 2 weeks for a total of 6 weeks along with standard anti-inflammatory treatment while the control group (n=10)  only received standard anti-inflammatory treatment. Anti-inflammatory treatment consisted of 1,000 mg/kg of methylprednisolone intravenously (IV) daily for 3 days and then 500 mg/kg for 2 days, followed by oral prednisone 1 mg/kg/day for 10 days. The dosage of prednisone was then reduced by 5 mg every 2 weeks until reaching a 5-mg/day maintenance dosage. After 1 year, the experimental group demonstrated significantly less relapse rate than the control group. The EDSS was significantly different from 2 months after treatment to the end of follow up at 1 year after treatment. Human umbilical cord mesenchymal stem cells administered intravenously in conjunction with standard anti-inflammatory treatment was significantly more efficacious than anti-inflammatory medication alone in preventing disease relapse and improving EDSS scores when evaluated 1 year after treatment.
• Riordan NH, Morales I, Fernández G, Allen N, Fearnot NE, Leckrone ME, Markovich DJ, Mansfield D, Avila D, Patel AN, Kesari S, Paz Rodriguez J. Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis. J Transl Med. 2018 Mar 9;16(1):57. doi: 10.1186/s12967-018-1433-7. Erratum in: J Transl Med. 2021 May 10;19(1):197. PMID: 29523171; PMCID: PMC5845260.
  Dr. Riordan’s clinical trial in Panama treated 20 patients with 7 doses of 20x10^6 cultured umbilical mesenchymal stem cells intravenously over 7 days. Patients were evaluated at 1 month and 1 year after treatment. The initial EDSS average was 5.23. This statistically significantly improved to an average of 4.75 and 4.62 at 1 and 12 months, respectively.  Cultured umbilical mesenchymal stem cells administered intravenously demonstrated efficacy in reducing the EDSS by one month and this improvement was sustained for at least 12 months.
• Xu J, Ji BX, Su L, Dong HQ, Sun WL, Wan SG, Liu YO, Zhang P, Liu CY. Clinical outcome of autologous peripheral blood stem cell transplantation in opticospinal and conventional forms of secondary progressive multiple sclerosis in a Chinese population. Ann Hematol. 2011 Mar;90(3):343-8. doi: 10.1007/s00277-010-1071-5. Epub 2010 Sep 25. PMID: 20872003.
  Dr. Xu’s clinical trial studied 35 patients, 20 of which were diagnosed with opticospinal multiple sclerosis and 15 had conventional multiple sclerosis. They were treated with autologous stem cells from peripheral blood after mobilization with Filgastrim. The dose of the infusion was 3.19x10^8 nucleated cells/kg, administered by IV. 2 years after treatment, the average EDSS score significantly improved from 6.37 to 5.73 in the opticospinal multiple sclerosis group. 13/15 patients in the conventional multiple sclerosis group demonstrated efficacy in neurological improvement as measured by the EDSS. Stem cell mobilization and intravenous infusion demonstrated improvement in multiple sclerosis symptoms, as measured by EDSS, in patients with both opticospinal and conventional multiple sclerosis when evaluated 2 years after treatment.

Click here for the clinical trial for Multiple Sclerosis

Multiple System Atrophy

• Singer, W., Dietz, A. B., Zeller, A. D., Gehrking, T. L., Schmelzer, J. D., Schmeichel, A. M., Gehrking, J. A., Suarez, M. D., Sletten, D. M., Minota Pacheco, K. V., Coon, E. A., Sandroni, P., Benarroch, E. E., Fealey, R. D., Matsumoto, J. Y., Bower, J. H., Hassan, A., McKeon, A., Windebank, A. J., Mandrekar, J. N., … Low, P. A. (2019). Intrathecal administration of autologous mesenchymal stem cells in multiple system atrophy. Neurology, 93(1), e77–e87. https://doi.org/10.1212/WNL.0000000000007720

24 multiple system atrophy patients received between 10 and 200 million adipose derived autologous MSCs delivered intrathecally. There were no serious adverse events. At the highest dose, ¾ patients experienced leg pain and it was determined that dose-limited toxicity was reached. The rate of progression of disease was lower for the MSC groups as compared to historical control, but more studies should be conducted.

• Lee, P. H., Lee, J. E., Kim, H. S., Song, S. K., Lee, H. S., Nam, H. S., Cheong, J. W., Jeong, Y., Park, H. J., Kim, D. J., Nam, C. M., Lee, J. D., Kim, H. O., & Sohn, Y. H. (2012). A randomized trial of mesenchymal stem cells in multiple system atrophy. Annals of neurology, 72(1), 32–40. https://doi.org/10.1002/ana.23612

33 patients with multiple system atrophy (cerebellar type) were randomly assigned to receive either 40 million MSCs intra-arterially or intravenously or a placebo. The MSC group had a smaller increase in UMSARS part II scores compared to placebo. This indicates that MSC treatment could delay the neurological deficit progression in MSA.

• Lee, P. H., Kim, J. W., Bang, O. Y., Ahn, Y. H., Joo, I. S., & Huh, K. (2008). Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy. Clinical pharmacology and therapeutics, 83(5), 723–730. https://doi.org/10.1038/sj.clpt.6100386

11 patients were treated with MSCs for multiple system atrophy, compared to 18 patients treated with a control. The MSC patients had significantly higher improvement than the control patients. MSC treatment delayed the progression of neurological deficits in MSA patients.

Osteoarthritis

• Lee, W. S., Kim, H. J., Kim, K. I., Kim, G. B., & Jin, W. (2019). Intra-Articular Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo-Controlled Clinical Trial. Stem cells translational medicine, 8(6), 504–511. https://doi.org/10.1002/sctm.18-0122

12 patients underwent autologous adipose-derived MSC treatment, injected intra-articularly into 12 knees. 12 knees were injected with saline, acting as the control. A single injection led to significant WOMAC improvement at 6 months. There was no significant WOMAC improvement in the control group. There was no significant change in cartilage defect for the MSC group after 6 months while there was a significant increase in defect for the control group after 6 months. This study demonstrates that intra-articular injections of MSCs for knee osteoarthritis significantly improves pain scores and prevents continued cartilage defect.

• Freitag, J., Bates, D., Wickham, J., Shah, K., Huguenin, L., Tenen, A., Paterson, K., & Boyd, R. (2019). Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regenerative medicine, 14(3), 213–230. https://doi.org/10.2217/rme-2018-0161

30 patients with knee osteoarthritis were divided into 3 groups. 2 treatment groups received an intra-articular injection of adipose derived MSCs (either one dose of 1 million cells at baseline or a dose of 1 million cells at baseline and an additional dose of 1 million cells after 6 months). The third group underwent conservative management, serving as a control. The MSC groups both showed clinically significant pain reduction and functional improvement at the 12 month follow up.

• Jo, C. H., Lee, Y. G., Shin, W. H., Kim, H., Chai, J. W., Jeong, E. C., Kim, J. E., Shim, H., Shin, J. S., Shin, I. S., Ra, J. C., Oh, S., & Yoon, K. S. (2014). Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem cells (Dayton, Ohio), 32(5), 1254–1266. https://doi.org/10.1002/stem.1634

18 patients with knee osteoarthritis were enrolled in this study. Phase one of the study had 3 groups of 3 patients, receiving either a low dose (1x10^7 cells), mid-dose (5x10^7 cells), or high dose (1x10^8 cells). The second phase enrolled 9 patients all receiving the high dose. After 6 months, the high-dose group experienced significant improvement in pain and knee function.

• Lamo-Espinosa, J. M., Mora, G., Blanco, J. F., Granero-Moltó, F., Núñez-Córdoba, J. M., López-Elío, S., Andreu, E., Sánchez-Guijo, F., Aquerreta, J. D., Bondía, J. M., Valentí-Azcárate, A., Del Consuelo Del Cañizo, M., Villarón, E. M., Valentí-Nin, J. R., & Prósper, F. (2018). Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II). Journal of translational medicine, 16(1), 213. https://doi.org/10.1186/s12967-018-1591-7

30 patients with knee osteoarthritis were assigned to receive either intra-articularly administered HA, HA plus 1 million bone marrow MSCs, or 100 million bone marrow MSCs alone. No adverse events were reported at the 4 years follow up. The bone marrow MSCs group had clinically significant improvements in WOMAC.

• Chen, C. F., Hu, C. C., Wu, C. T., Wu, H. H., Chang, C. S., Hung, Y. P., Tsai, C. C., & Chang, Y. (2021). Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE®: a phase I/II, randomized, active-control, single-blind, multiple-center clinical trial. Stem cell research & therapy, 12(1), 562. https://doi.org/10.1186/s13287-021-02631-z

57 subjects were randomized into 4 different groups: one group receiving a hyaluronic acid control and 3 groups receiving doses of adipose derived stem cells. At the week 24 follow up, both groups had improvements in WOMAC score but the stem cell group also had significant improvements after 4 weeks. The stem cell group pain scores after 48 weeks suggest a longer duration of effectiveness compared to the HA group.

• Matas, J., Orrego, M., Amenabar, D., Infante, C., Tapia-Limonchi, R., Cadiz, M. I., Alcayaga-Miranda, F., González, P. L., Muse, E., Khoury, M., Figueroa, F. E., & Espinoza, F. (2019). Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial. Stem cells translational medicine, 8(3), 215–224. https://doi.org/10.1002/sctm.18-0053

Patients were randomized to receive either HA at baseline and 6 months, a single dose of 20 million umbilical cord MSCs at baseline, or 2 doses of 20 million umbilical cord MSCs at baseline and 6 months. The MSC-treated patients experienced significant improvements in pain and function from baseline while the HA group did not. The pain score for the 2-dose group was significantly lower than the HA group at 12 months.

Parkinson’s Disease

• Madrazo I, Kopyov O, Ávila-Rodríguez MA, Ostrosky F, Carrasco H, Kopyov A, Avendaño-Estrada A, Jiménez F, Magallón E, Zamorano C, González G, Valenzuela T, Carrillo R, Palma F, Rivera R, Franco-Bourland RE, Guízar-Sahagún G. Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after Surgery. Cell Transplant. 2019 Mar;28(3):269-285. doi: 10.1177/0963689718820271. Epub 2018 Dec 21. PMID: 30574805; PMCID: PMC6425108.
  Dr. Madrazo’s case series study follows 8 patients with moderate PD. Undifferentiated neural progenitor cells from fetal brain tissue were injected into the patients’ dorsal putamina. The patients were followed up with for 4 years.
  After 1 year, 6/7 patients showed some degree of motor improvement and 5/7 showed better response to medication. PET imaging showed a trend towards enhanced midbrain dopaminergic activity. At 4 years, improvements had revered but were still better than baseline.
• Venkataramana NK, Kumar SK, Balaraju S, Radhakrishnan RC, Bansal A, Dixit A, Rao DK, Das M, Jan M, Gupta PK, Totey SM. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson's disease. Transl Res. 2010 Feb;155(2):62-70. doi: 10.1016/j.trsl.2009.07.006. Epub 2009 Aug 6. PMID: 20129486.
  7 patients treated with autologous bone marrow derived mesenchymal stem cells. Stem cells were transplanted into the sublateral ventricular zone. 
• Lige L, Zengmin T. Transplantation of Neural Precursor Cells in the Treatment of Parkinson Disease: An Efficacy and Safety Analysis. Turk Neurosurg. 2016;26(3):378-83. doi: 10.5137/1019-5149.JTN.10747-14.4. PMID: 27161464.
  21 patients enrolled in this study. Treatment included embryonic stem cells that were cultured and differentiated to become neural precursor cells and dopaminergic neurons. Cells were injected directly into the striatum. The average decrease in unified parkinsons disease rating scale decreased from 80.7 to 72.6, with similar improvement in all the subcategories of the scale. Additionally, the Schwab-England scale showed statistically significant improvement before and after treatment. Improvement was seen for up to 57 months after transplantation.  Cultured and differentiated embryonic stem cells administered directly into the striatum showed improvement in parksinson’s disease rating scales. Improvement was seen for up to 57 months. 

Rheumatoid arthritis

• Wang L, Huang S, Li S, Li M, Shi J, Bai W, Wang Q, Zheng L, Liu Y. Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy for Rheumatoid Arthritis Patients: A Prospective Phase I/II Study. Drug Des Devel Ther. 2019 Dec 19;13:4331-4340. doi: 10.2147/DDDT.S225613. PMID: 31908418; PMCID: PMC6930836.
  Dr. Wang’s clinical trial studied 64 RA patients treated with 40 mL UC-MSC suspension product (2 × 10⁷ cells/20 mL) via intravenous injection immediately after the infusion of 100 mL saline.  DAS 28 decreased significantly from around (4.2 pre treatment to 3.2 at 1 year and 3 at 2 years). HAQ scores decreased significantly from around (5 pre treatment to 2 at 1 year and 1 at 2 years). Intravenous injection of umbilical cord mesenchymal stem cells demonstrated efficacy in reducing symptoms associated with RA, with sustained long term improvement up to two years.
• Ghoryani M, Shariati-Sarabi Z, Tavakkol-Afshari J, Ghasemi A, Poursamimi J, Mohammadi M. Amelioration of clinical symptoms of patients with refractory rheumatoid arthritis following treatment with autologous bone marrow-derived mesenchymal stem cells: A successful clinical trial in Iran. Biomed Pharmacother. 2019 Jan;109:1834-1840. doi: 10.1016/j.biopha.2018.11.056. Epub 2018 Nov 26. PMID: 30551438.
  Dr. Ghoryani studied 9 refractory RA patients treated with one IV dose of 1x10^6 cultured auto BM-MSC’s per kg. The patients were followed up for 12 months.  Mean DAS28 decreased significantly from 5.02 pre treatment to 4.45 at 1 month and 4.25 at 12 months. Mean VAS score decreased significantly from 7.77 pre treatment to 6.88 at one month and 5.66 at 12 months. Intravenous infusion of cultured autologous bone marrow derived mesenchymal stem cells demonstrated efficacy in improving symptoms associated with RA along with decreasing pain at 12 month follow up.
• Shadmanfar S, Labibzadeh N, Emadedin M, Jaroughi N, Azimian V, Mardpour S, Kakroodi FA, Bolurieh T, Hosseini SE, Chehrazi M, Niknejadi M, Baharvand H, Gharibdoost F, Aghdami N. Intra-articular knee implantation of autologous bone marrow-derived mesenchymal stromal cells in rheumatoid arthritis patients with knee involvement: Results of a randomized, triple-blind, placebo-controlled phase 1/2 clinical trial. Cytotherapy. 2018 Apr;20(4):499-506. doi: 10.1016/j.jcyt.2017.12.009. Epub 2018 Feb 7. PMID: 29428486.
  Dr. Shadmanfar’s clinical trial followed 30 patients, 15 of which were treated with 40 million cultured auto BM-MSC’s intra-articularly.  WOMAC pain score decreased to -16.5 in the MSCs group compared to -6.7 in control. VAS score decreased by more than 50% in the MSC s group (-2.2 MSCs vs -1.7 control). After 12 months of follow up, any improvement was not significantly sustained.

Click here for the clinical trial for Rheumatoid Arthriris

Sarcoidosis

• Baughman RP, Culver DA, Jankovi V, Fischkoff S, Brockway G, Lower EE. Placenta-derived mesenchymal-like cells (PDA-001) as therapy for chronic pulmonary sarcoidosis: a phase 1 study. Sarcoidosis Vasc Diffuse Lung Dis. 2015 Jul 22;32(2):106-14. PMID: 26278689.
  4 patients with chronic pulmonary sarcoidosis were recruited for this study. Each patient received two infusion of 150 million placenta derived mesenchymal like stem cells. After a year, there were no significant changes in FVC but two patients had improvement on their chest x-ray and had steroid sparing benefits. Two infusions of placenta derived mesenchymal like stem cells resulted in 2/4 patients showing benefit on CXR and reduction in steroid requirements after 1 year. There were no changes in FVC.
• McClain Caldwell I, Hogden C, Nemeth K, Boyajian M, Krepuska M, Szombath G, MacDonald S, Abshari M, Moss J, Vitale-Cross L, Fontana JR, Mezey E. Bone Marrow-Derived Mesenchymal Stromal Cells (MSCs) Modulate the Inflammatory Character of Alveolar Macrophages from Sarcoidosis Patients. J Clin Med. 2020 Jan 19;9(1):278. doi: 10.3390/jcm9010278. PMID: 31963936; PMCID: PMC7019909.
  15 patients with sarcoidosis and 9 controls underwent bronchoalveolar lavage. Bronchoalveolar lavage cells (70-94%) macrophages were isolated and cultured with allogeneic bone marrow derived MSCs. The medium was examined after the co-culture. In sarcoidosis patients, coculture with MSCs resulted in a reduction in TNF-alpha and an increase in IL-10. Additionally, flow cytometry revealed a reduction in M1 macrophages and an increase in M2 macrophages, indicating an anti-inflammatory state. Coculture of allogeneic bone marrow derived MSCs with sarcoidosis patient macrophages resulted in a decrease in TNF-alpha, increase in IL-10 and transition from M1 to M2 macrophages, indicating an anti-inflammatory state.

Scleroderma

• Granel B, Daumas A, Jouve E, Harlé JR, Nguyen PS, Chabannon C, Colavolpe N, Reynier JC, Truillet R, Mallet S, Baiada A, Casanova D, Giraudo L, Arnaud L, Veran J, Sabatier F, Magalon G. Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial. Ann Rheum Dis. 2015 Dec;74(12):2175-82. doi: 10.1136/annrheumdis-2014-205681. Epub 2014 Aug 11. PMID: 25114060; PMCID: PMC4680117.

Dr. Granel followed 12 patients diagnosed with systemic sclerosis. The patients were treated with autologous adipose derived-SVF at a dose of 3.78x10^6 cells administered directly into each finger. Conchin Hand Function Scale showed a significant improvement of 47.4% at 2 months and 56% at 6 months. Grip strength and pinch strength at 6 months showed a significant improvement in both dominant and non-dominant hands. The global modified rodnan skin score decreased significantly at 2 and 6 months when compared to baseline. Raynoud Condition Score and hand pain also showed statistically significant improvement at 2 and 6 months, Injection of SVF directly into the digits in patients with scleroderma demonstrated efficacy in improving function, strength, skin thickness, raynoud’s symptoms and pain at 2 and 6 months.

• Guillaume-Jugnot P, Daumas A, Magalon J, Jouve E, Nguyen PS, Truillet R, Mallet S, Casanova D, Giraudo L, Veran J, Dignat-George F, Sabatier F, Magalon G, Granel B. Autologous adipose-derived stromal vascular fraction in patients with systemic sclerosis: 12-month follow-up. Rheumatology (Oxford). 2016 Feb;55(2):301-6. doi: 10.1093/rheumatology/kev323. Epub 2015 Sep 8. PMID: 26350489.

Dr. Guillaume-Jugnot’s clinical trial followed 12 patients for 12 months after treatment with SVF injected into the subcutaneous tissue of each digit. From the lipoaspiration, an average of 50.5x10^6 total viable nucleated cells was obtained. At 12 month follow up, Conchin Hand Functional Scale, Raynoud Condition Score, hand strength, mean circumference of fingers and pain scores all demonstrated statistically significant improvement. Injection of SVF into the subcutaneous space of the digits resulted in significant functional improvement and pain reduction in patients with scleroderma when evaluated 12 months after treatment.  

• Del Papa N, Di Luca G, Andracco R, Zaccara E, Maglione W, Pignataro F, Minniti A, Vitali C. Regional grafting of autologous adipose tissue is effective in inducing prompt healing of indolent digital ulcers in patients with systemic sclerosis: results of a monocentric randomized controlled study. Arthritis Res Ther. 2019 Jan 7;21(1):7. doi: 10.1186/s13075-018-1792-8. PMID: 30616671; PMCID: PMC6322261.

Dr. del Papa’s study enrolled 38 patients with digital ulcers secondary to systemic sclerosis. 25 were treated with .5-1mL of autologous adipose tissue injected at the base of the finger that had the ulcer. The other 13 patients underwent sham procedures. 92% of patients in the treatment group demonstrated distal ulcer healing after 8 weeks. This was compared with only 7.7% of patients who had healing ulcers in the control group. The difference was highly statistically significant. After 8 weeks, all 12 patients who had ulcers in the control group that did not heal received the treatment therapy. In the following 8 weeks, all 12 of these patients had evidence of ulcer healing. Treatment was also associated with a significant reduction in pain scores and also was significantly associated with increased capillaries in the affected digits. Injection of autologous adipose tissue into the base of a digit with a distal ulcer demonstrated increased healing, reduced pain and increased capillary number within 8 weeks compared to placebo.

Click here for the clinical trial for Scleroderma

Sjogren’s Syndrome

• Xu J, Wang D, Liu D, Fan Z, Zhang H, Liu O, Ding G, Gao R, Zhang C, Ding Y, Bromberg JS, Chen W, Sun L, Wang S. Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjögren syndrome. Blood. 2012 Oct 11;120(15):3142-51. doi: 10.1182/blood-2011-11-391144. Epub 2012 Aug 27. PMID: 22927248; PMCID: PMC3471521.

24 patients with sjogren’s syndrome were enrolled in this study and treated with an intravenous infusion of 1x10^6/kg cultured allogeneic umbilical cord derived mesenchymal stem cells. No serious adverse events occurred. All patients showed improvement, with a response time ranging from 2 weeks to 6 months. At 12 months, 83% of patients had their sjogren’s syndrome disease activity index decrease by greater than 30% from baseline. At 12 months, 75% of patients’ VAS score decreased by greater than 30%. Patients suffering from specific disease processes including decreased salivary flow rate and organ specific involvement showed significant improvement in salivary flow rate and organ specific indexes within the 12 month follow up. The only organ system not to show significant improvement was the nervous system. Intravenous infusion of allogeneic cultured umbilical cord derived mesenchymal stem cells resulted in significant improvement in pain and disease activity indexes. All organ systems involved showed significant improvement, except the nervous system. No treatment related adverse events occurred.

Spinal Cord Injury with Paralysis

• Bydon M, Dietz AB, Goncalves S, Moinuddin FM, Alvi MA, Goyal A, Yolcu Y, Hunt CL, Garlanger KL, Del Fabro AS, Reeves RK, Terzic A, Windebank AJ, Qu W. CELLTOP Clinical Trial: First Report From a Phase 1 Trial of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury. Mayo Clin Proc. 2020 Feb;95(2):406-414. doi: 10.1016/j.mayocp.2019.10.008. Epub 2019 Nov 27. PMID: 31785831.
  Dr. Bydon’s clinical trial at the Mayo Clinic studied 1 patient age 53, who suffered a C3-C4 spinal cord injury with complete loss of motor and sensation below the level of the injury. The patient had an associated loss of bowel and bladder sensation. He underwent a C2-C6 posterior cervical decompression and fusion with subsequent improvement in sensation, motor and bowel and bladder function. 6 months after the operation the progress plateaued. The patient was treated with 1 dose of 100 million adipose derived mesenchymal stem cells, administered intrathecally. The total upper extremity ASIA motor score improved from 35 at baseline to 44 after 18 months. Lower extremity ASIA motor score improved from 36 at baseline to 49 at 18 months. The total ASIA sensory pinprick score improved from 45 at baseline to 95 at 18 months. ASIA sensory total light touch score improved from 54 at baseline to 96 at 18 months. Intrathecal injection of 100 million adipose derived mesenchymal stem cells demonstrated the ability to significantly improve upper extremity motor function, lower extremity motor function, pinprick sensation and light touch scores in a patient suffering from cervical spinal cord injury 18 months after treatment.
• Cheng H, Liu X, Hua R, Dai G, Wang X, Gao J, An Y. Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury. J Transl Med. 2014 Sep 12;12:253. doi: 10.1186/s12967-014-0253-7. PMID: 25209445; PMCID: PMC4172930.
  Dr. Cheng’s trial enrolled 34 patients with T10-L1 injuries. 10 patients received 4x10^7 cultured umbilical cord mesenchymal stem cells injected into the spinal cord, 14 patients received standard rehabilitation and 10 patients received no intervention.  For the umbilical cord group, compared to baseline, motion significantly improved from 54 to 58, excessive muscle tension decreased from 9.9 to 8.5 and Barthel Index increased from 33.5 to 41.4. The patients in the rehabilitation group and the control group did not show significant improvement in any of the parameters and the control group worsened in all the parameters. None of the groups showed significant improvement in sensation but the UC improved from 146.6 to 148.3 while the other two groups worsened in this parameter. Administration of 4x10^7 umbilical cord mesenchymal stem cells into the spinal cord improved motion, muscle tension and ability to perform activities of daily living when reevaluated 6 months after treatment. Treatment also demonstrated minimal improvement in sensation while control group continued to deteriorate in these categories.
• Dai G, Liu X, Zhang Z, Yang Z, Dai Y, Xu R. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Res. 2013 Oct 2;1533:73-9. doi: 10.1016/j.brainres.2013.08.016. Epub 2013 Aug 12. PMID: 23948102.
  Dr. Dai’s clinical trial enrolled 40 patients with cervical spinal cord injuries. 20 of the patients were treated with 25uL of 8x10^5 cells/uL of autologous cultured bone marrow derived mesenchymal stem cells administered directly into the lesion. The other 20 patients were controls. The patients were followed for 6 months. The experimental group showed a total ASIA score improvement from 31.6 to 43.1 from baseline to 6 months after treatment. Additionally, each of the individual components of the ASIA score also demonstrated statistically significant improvement. The control group demonstrated no statistically significant improvement in any components of the ASIA score. Autologous cultured bone marrow derived mesenchymal stem cells administered directly into the site of injury showed to be efficacious in improving all components of ASIA score when assessed 6 months after treatment.
• Hur JW, Cho TH, Park DH, Lee JB, Park JY, Chung YG. Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial. J Spinal Cord Med. 2016 Nov;39(6):655-664. doi: 10.1179/2045772315Y.0000000048. Epub 2015 Jul 24. PMID: 26208177; PMCID: PMC5137573.
  Dr. Hur’s trial followed 14 patients with all levels of injury. They were treated with three doses of autologous adipose-derived stem cells at a dose of 3x10^7 given intrathecally. Prior to injection, the cells were cultured and supplemented with 10% fetal bovine serum and 1ng/ml human basic fibroblast growth factor. The patients were followed for 8 months after injection.  At 8 months, 5 patients improved motor scores, 2 patients improved voluntary anal contraction, 10 improved sensory and 1 had median nerve improvement. Repetitive intrathecal injection of cultured and differentiated adipose derived mesenchymal stem cells demonstrated mild improvements in motor, anal contraction and sensation in patients with spinal cord injuries when evaluated 8 months after treatment.
• Liu J, Han D, Wang Z, Xue M, Zhu L, Yan H, Zheng X, Guo Z, Wang H. Clinical analysis of the treatment of spinal cord injury with umbilical cord mesenchymal stem cells. Cytotherapy. 2013 Feb;15(2):185-91. doi: 10.1016/j.jcyt.2012.09.005. PMID: 23321330.
  Dr. Liu studied 22 patients treated with allogeneic umbilical cord mesenchymal stem cells at a dose of 1x10^6 per kg once a week for 4 weeks administered intrathecally. Before and 1 month after treatment assessments in total ASIA score and IANR-SCIFRS scores showed statistically significant improvement. When further stratified, it was noted that patients with incomplete spinal cord injuries showed statistically significant improvement in motor function, algesia, sensory function and activities of daily living one month after treatment compared to baseline. The patients with complete spinal cord injury demonstrated no improvement in any of the parameters. Allogeneic umbilical cord mesenchymal stem cells demonstrated efficacy in improving symptoms with incomplete spinal cord injury when evaluated 1 month after treatment. Those with complete spinal cord injury demonstrated no improvement.
• Mendonça MV, Larocca TF, de Freitas Souza BS, Villarreal CF, Silva LF, Matos AC, Novaes MA, Bahia CM, de Oliveira Melo Martinez AC, Kaneto CM, Furtado SB, Sampaio GP, Soares MB, dos Santos RR. Safety and neurological assessments after autologous transplantation of bone marrow mesenchymal stem cells in subjects with chronic spinal cord injury. Stem Cell Res Ther. 2014 Nov 17;5(6):126. doi: 10.1186/scrt516. PMID: 25406723; PMCID: PMC4445989.
  Dr. Mendonca studied 14 patients diagnosed with complete spinal cord injury. The patients were treated with cultured autologous bone marrow derived mesenchymal stem cells at a dose of 5x10^6 per cm^3 per lesion volume. There was a statistically significant improvement in ASIA light touch and pinprick scores. Additionally, there was a significant improvement in ASIA motor scores when evaluated at 6 months compared to baseline. 6 month evaluation also demonstrated significant improvement in bladder compliance. Cultured autologous bone marrow mesenchymal stem cells administered directly into the lesion demonstrated improvement in all components of ASIA score along with bladder compliance when evaluated 6 months after treatment.
• Vaquero J, Zurita M, Rico MA, Bonilla C, Aguayo C, Fernández C, Tapiador N, Sevilla M, Morejón C, Montilla J, Martínez F, Marín E, Bustamante S, Vázquez D, Carballido J, Rodríguez A, Martínez P, García C, Ovejero M, Fernández MV; Neurological Cell Therapy Group. Repeated subarachnoid administrations of autologous mesenchymal stromal cells supported in autologous plasma improve quality of life in patients suffering incomplete spinal cord injury. Cytotherapy. 2017 Mar;19(3):349-359. doi: 10.1016/j.jcyt.2016.12.002. Epub 2017 Jan 6. PMID: 28089079.
  Dr. Vaquero enrolled 10 patients diagnosed with incomplete SCI. The patients were treated with 4 doses of autologous bone marrow derived mesenchymal stem cells. They received 4 doses, each consisting of 30x10^6 mesenchymal stem cells administered at an interval 3 months apart. The cells were injected intrathecally and the patients were followed for 12 months. The average total ASIA score significantly improved after the 1^st injection and continued to progress throughout the duration of the study. Total ASIA score at baseline was 188 and progressed to 235 at 12 month follow up. The subcategories including pin prick sensation, light touch and motor score all demonstrated the same trend, showing significant improvement after the first treatment and maximal improvement at 12 month follow up. The patients also showed a significant early and progressive neurogenic bowel dysfunction rating score along with bladder compliance. Repeat intrathecal injection of autologous bone marrow derived mesenchymal stem cells demonstrated efficacy in improving all components of ASIA score, along with bowel and bladder function when evaluated 12 months after treatment. Additionally, repetitive treatment showed to have additive benefit.
• Vaquero J, Zurita M, Rico MA, Aguayo C, Bonilla C, Marin E, Tapiador N, Sevilla M, Vazquez D, Carballido J, Fernandez C, Rodriguez-Boto G, Ovejero M; Neurological Cell Therapy Group from Puerta de Hierro-Majadahonda Hospital. Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline. Cytotherapy. 2018 Jun;20(6):806-819. doi: 10.1016/j.jcyt.2018.03.032. Epub 2018 May 28. PMID: 29853256.
  Dr. Vaquero’s clinical trial had 9 patients treated with cultured autologous bone marrow MSC’s. Each patient received 3 doses of 100x10^6 cells given intrathecally. The dosing interval was every 3 months. They were followed for 10 months. The average total ASIA score significantly improved after the 1^st injection and continued to progress throughout the duration of the study. Total ASIA score at baseline was 182 and progressed to 204 at 4 months, 213 at 7 months and 217 at 10 months. The subcategories including pin prick sensation, light touch and motor score all demonstrated the same trend. Repeat intrathecal injection of autologous bone marrow derived mesenchymal stem cells demonstrated efficacy in improving all components of ASIA score, along with bowel and bladder function when evaluated 10. Additionally, repetitive treatment showed to have additive benefit.
• Vaquero J, Zurita M, Rico MA, Bonilla C, Aguayo C, Montilla J, Bustamante S, Carballido J, Marin E, Martinez F, Parajon A, Fernandez C, Reina L; Neurological Cell Therapy Group. An approach to personalized cell therapy in chronic complete paraplegia: The Puerta de Hierro phase I/II clinical trial. Cytotherapy. 2016 Aug;18(8):1025-1036. doi: 10.1016/j.jcyt.2016.05.003. Epub 2016 Jun 13. PMID: 27311799.
  Dr. Vaquero treated 12 patients with complete paraplegia. The patients were treated with cultured autologous bone marrow mesenchymal stem cells at a dose of 100-230x20^6 intramedullary directly into the damaged spinal cord tissue, then 3 months later they received a second injection of 30x10^6 cells intrathecally, around the level of the injury.  Patients were followed for 12 months. The cohort demonstrated a statistically significant improvement in motor score of the lower extremity. 30% of the patients who were diagnosed with complete spinal cord lesion before treatment (ASIA A) were subsequently characterized as ASIA B or C representing an incomplete lesion. Average total ASIA score went from 165.9 to 213.25 from baseline to 12 months after treatment. Additionally, all 8 parameters of the IANR-SCIFRS scale significantly improved from baseline to 12 months. Intramedullary in conjunction with intrathecal injection of cultured autologous bone marrow derived mesenchymal stem cells demonstrated significant improvement in all components of ASIA score and IANR-SCIFRS scale when evaluated 12 months after treatment.
• Geffner LF, Santacruz P, Izurieta M, Flor L, Maldonado B, Auad AH, Montenegro X, Gonzalez R, Silva F. Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell Transplant. 2008;17(12):1277-93. doi: 10.3727/096368908787648074. PMID: 19364066.
  Eight paraplegic patients with thoracic cord injuries had infusion of bone marrow stem cells and mononuclear cells.  Cells were administered iv and by open intrathecal injection.  There were 4 chronic and 4 acute spinal cord injury patients.  Barthel scores, ASIA and bladder scores increased significantly for all 8 patients, with improvement maximal at 6 months but maintained to 2 years.  Mean Barthel improvement was more than 40 points out of 100.
  Intrathecal instillation of bone marrow cells produce substantial lasting improvement in paraplegic patients in ASIA, Barthel and bladder scores, maintained to final follow up at 2 years.

Traumatic brain injury

• Wang S, Cheng H, Dai G, Wang X, Hua R, Liu X, Wang P, Chen G, Yue W, An Y. Umbilical cord mesenchymal stem cell transplantation significantly improves neurological function in patients with sequelae of traumatic brain injury. Brain Res. 2013 Sep 26;1532:76-84. doi: 10.1016/j.brainres.2013.08.001. Epub 2013 Aug 11. PMID: 23942181.
  40 patients with sequelae of TBI were included in this study. Half of the patients were controls and other half received 4 doses of umbilical cord mesenchymal stem cells by lumbar puncture. At 6 months the control group did not show any improvement in any of the parameters measured. At 6 months, the experimental group demonstrated significant improvement in FMA (and individual sub-scores including: upper extremity motor, lower extremity motor, sensation and balance). Additionally the experimental group showed significant improvement in FIM ( and sub-scores including: patient self-care, sphincter control, mobility, locomotion, communication and social cognition). Umbilical cord mesenchymal stem cells administered intrathecally demonstrated significant improvement at 6 months in the FMA and FIM assessments, including their sub-scores. Patients assigned to the control group demonstrated no improvement in these parameters.
• Tian C, Wang X, Wang X, Wang L, Wang X, Wu S, Wan Z. Autologous bone marrow mesenchymal stem cell therapy in the subacute stage of traumatic brain injury by lumbar puncture. Exp Clin Transplant. 2013 Apr;11(2):176-81. doi: 10.6002/ect.2012.0053. Epub 2012 Aug 11. PMID: 22891928.
  97 patients were included in this study, 24 of which were in a vegetative state and 73 had deficits in motor activity. Patients were treated with cultured autologous bone marrow derived mesenchymal cells administered intrathecally. 27 of the 73 patients who had deficits in motor activity showed improvement in motor functions. The responders with hemiplegic paralysis showed increased motor power and the patients with muscle spasticity expressed partial muscle relaxation. 11 of the 24 patients in a vegetative state demonstrated post-therapeutic improvements in consciousness. This included increased eyeball tracking, groaning, responsive tearing and swallowing fluid. 45.8% of patients in vegetative state and 37% of patients with motor disorders demonstrated improvement in symptoms after treatment with autologous cultured bone marrow derived mesenchymal stem cells administered intrathecally when assessed 14 days after treatment.
• Wang Z, Luo Y, Chen L, Liang W. Safety of neural stem cell transplantation in patients with severe traumatic brain injury. Exp Ther Med. 2017 Jun;13(6):3613-3618. doi: 10.3892/etm.2017.4423. Epub 2017 May 4. PMID: 28588689; PMCID: PMC5450816.
  10 patients with severe traumatic brain injury were included in this study. Autologous bone marrow was cultured and differentiated into neural stem cells. 7 patients received intravenous infusion and 3 patients received intrathecal injections. 60 days after treatment, all patients showed improvement in NIHSS scores (10 to 22 points in improvement) and GCS score (2-8 points in improvement). Additionally, average serum levels of NGF and BDNF significantly increased when reassessed 7 days after treatment. Cultured and differentiated autologous bone marrow derived mesenchymal stem cells administered intravenously demonstrated clinical improvements 60 days after treatment and increase in neurotrophic factors when evaluated 7 days after treatment.

Click here for the clinical trial for Traumatic brain injury