FEASIBILITY, SAFETY, AND EFFICACY OF AUTOLOGOUS ADIPOSE-DERIVED MESENCHYMAL STROMAL CELLS ADHERED TO TYPE I/III COLLAGEN MEMBRANE FOR FOCAL KNEE CARTILAGE DEFECTS: A PHASE 1 CLINICAL TRIAL

Abstract

Background & Aim

Mesenchymal stromal cell (MSC) transplantation has shown promising outcomes in treating focal chondral defects of the knee, providing notable improvements in pain and functional scores. This study aims to assess the feasibility, safety, and efficacy of a Tissue Engineering Product (TEP) utilizing autologous adipose tissue (AT)-MSCs associated to a type I/III collagen membrane for the treatment of symptomatic focal cartilage defects in knee.

Methods, Results & Conclusion

Four patients with full-thickness knee cartilage defects received TEP implantation and were prospectively followed by 12 months. Autologous subcutaneous adipose tissue was harvested and transported to a private cell culture facility (StemCorp), where it was processed for cell isolation and expansion under a GMP system. Once characterized, the AT-MSC cells were associated to collagen type I/III membrane. Quality control tests were performed along the manufacture and for final TEP release. Knee surgery for TEP implantation was performed by arthrotomy, with the chondral defect prepared and the TEP sutured over the lesion with the help of fibrin glue. After surgery, all patients followed the same rehabilitation protocol. Safety of the procedure was assessed by the incidence of reoperations for any cause after TEP implantation, and by incidence and severity of complications. Efficacy was evaluated by means of clinical scales for functional status: International Knee Documentation Committee (IKDC); Knee injury and Osteoarthritis Outcome Score (KOOS); Lysholm Knee Scoring Scale, SF36 for quality life and Visual Analogue Scale (VAS) for pain intensity. Besides, patients were evaluated by magnetic resonance imaging (RMI) preoperatively and 12 months postoperatively. The study demonstrated the safety and feasibility of the TEP, with no reoperations or joint stiffness reported. After 12 months, substantial improvements were observed in functional scales (IKDC: 138%, KOOS: 92%, Lysholm: 53%), pain reduction (-72%), and quality of life (SF36 social functioning domain: 23%). Post-surgical MRI confirmed satisfactory tissue filling, resembling hyaline cartilage around the lesion according to the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) scale. This Phase 1 trial suggests that autologous AT-MSCs on a collagen membrane present a safe and effective approach for treating knee cartilage defects. The promising results warrant further exploration in larger clinical studies.