Summary

A scaffold-free tissue-engineered construct derived from autologous synovial mesenchymal stem cells could be used for regenerative cartilage repair via a suture-less and simple implantation procedure.

Abstract

Articular cartilage has limited healing capacity, due in part to poor vascularity and innervation. We originally developed a scaffold-free tissue-engineered construct (TEC) derived from autologous synovial membrane mesenchymal stem cells (MSCs) and demonstrated their safety and efficacy following implantation for cartilage repair at 2 years postoperatively in our earlier study. The present study aimed to further investigate clinical outcomes and MRI findings at 5 years post-implantation. An observational first-in-human study limited to 5 cases was approved by the Ministry of Health, Labor, and Welfare of Japan. Five patients (age 28 - 46 years old) with symptomatic knee chondral lesions (1.5 - 3.0 cm2) on the medial femoral condyle, lateral femoral condyle, or femoral groove were enrolled in this study. Synovial MSCs were isolated from arthroscopic biopsy specimens and cultured to develop a TEC that matched the lesion size. The TECs were then implanted into chondral defects without fixation and assessed up to 5 years postoperatively. The patients were clinically evaluated using a visual analog scale (VAS), Lysholm, Tegner, and Knee injury and Osteoarthritis Outcome Score (KOOS) scores. An MRI evaluation was also performed for morphologic and compositional quality of the repair tissue at 5 years of follow-up. All clinical scores were significantly improved from the preoperative evaluation to the 2- and 5-year follow-ups and the results were stable over time. The MRI evaluation showed cartilage defects filled with newly generated tissues with good tissue integration to adjacent host cartilage over time. The cartilage thickness and surface smoothness of the repair cartilage were maintained out to 5 years postoperatively. The MOCART 2.0 Knee Scores were maintained high at 5 years, although the total points decreased slightly. The present results highlighted the efficacy and feasibility of this procedure, showing good clinical outcomes and MRI findings with stable results at midterm follow-up. Thus, an autologous scaffold-free TEC derived from synovial MSCs could be used for regenerative cartilage repair via a suture-less and simple implantation procedure. On the other hand, further follow-up will be needed to assess the quality change in repair tissue.