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Accepted for oral presentation at the International Cartilage Repair Society Annual Meeting in Barcelona, Spain September 2023

Human pilot experience demonstrating the long-term regenerative properties of local immunomodulation associated with autologous stem cell therapy treatments for osteoarthritis of the knee and spine.

Moviglia GA, Moviglia-B MT, Bolander J, Piccone S, Updike T, Vaughan W, Mahajan N, Santacoloma E, Grangeat A, Kozima J, Ramirez R, Prodromos C, Atala A, Poheling G

Purpose: Demonstrate that the use of tissue-specific local immunomodulation associated with autologous stem cell implantation is necessary to regenerate tissues, control symptoms, improve joint function, and sustain its effects for more than 5 years.

Materials and methods: Between 2016 and 2018, the first human applications of local immunomodulation associated with autologous stem cells were carried out in patients with severe states of OA of the knee and spine. At the time, the safety of the therapy was studied using the questionnaire of adverse reactions of the NCI of US, the efficacy through the structural changes demonstrated by magnetic resonances of each joint treated, (in one of these patients it was corroborated by puncture biopsy of the area treated with greater damage) and the efficiency through functional indices (Koos, VAS and ODI respectively). The patients showed that the treatment was safe and showed clear signs of efficacy and efficiency. [Richardson et al Cytotherapy, 2019; 21(5):S93] [Grangeat et al Open J Orthop Rheumatol 2020, 5(1): 024-033}.

Results: In 2022, these patients were re-evaluated, showing that they remained with their positive effects, without requiring future treatments to recover the obtained benefits at one year after the first therapy. To explain this, in vitro and with Lewis rats experiments were carried out.

Activation of pro-repairing effector leukocytes (EC) for joints showed that they produce growth and differentiation factors for joint stem cells. The coculture of EC with AMSC induces, in 4 days, differentiated cartilage cells. The injection of a 24 hours coculture allowed recovery of cartilage, synovial membrane, and bone. subchondral, repopulating the specific area of the articular stem cell niche.

Conclusion: Preclinical and Clinical observations seem to show that the combination of local immunomodulation with the use of autologous stem cells can generate safe, effective and efficient reparative effects in osteoarthritic lesions.