Transplantation of synovial MSCs promoted healing after meniscal repair with induction of synovium into the longitudinal tear in the avascular zone of meniscus in pigs.

Transplantation of aggregates of synovial mesenchymal stem cells (MSCs) enhanced meniscus regeneration in rats. Anatomy and biological properties of the meniscus depend on animal species. To apply this technique clinically, it is valuable to investigate the use of animals genetically close to humans. We investigated whether transplantation of aggregates of autologous synovial MSCs promoted meniscal regeneration in aged primates. Chynomolgus primates between 12 and 13 years old were used. After the anterior halves of the medial menisci in both knees were removed, an average of 14 aggregates consisting of 250,000 synovial MSCs were transplanted onto the meniscus defect. No aggregates were transplanted to the opposite knee for the control. Meniscus and articular cartilage were analyzed macroscopically, histologically, and by MRI T1rho mapping at 8 (n = 3) and 16 weeks (n = 4). The medial meniscus was larger and the modified Pauli's histological score for the regenerated meniscus was better in the MSC group than in the control group in each primate at 8 and 16 weeks. Mankin's score for the medial femoral condyle cartilage was better in the MSC group than in the control group in all primates at 16 weeks. T1rho value for both the regenerated meniscus and adjacent articular cartilage in the MSC group was closer to the normal meniscus than in the control group in all primates at 16 weeks. Transplantation of aggregates of autologous synovial MSCs promoted meniscus regeneration and delayed progression of degeneration of articular cartilage in aged primates. This is the first report dealing with meniscus regeneration in primates. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1274-1282, 2017.

Background: Previous work has demonstrated that patients with cartilage defects of the knee benefit from arthroscopic transplantation of autologous synovial mesenchymal stem cells (MSCs) in terms of magnetic resonance imaging (MRI), qualitative histologic findings, and Lysholm score. However, the effectiveness was limited by the number of cells obtained, so large-sized defects (>500 mm2) were not investigated. The use of MSC aggregates may enable treatment of larger defects by increasing the number of MSCs adhering to the cartilage defect. Purpose: To investigate whether transplantation of aggregates of autologous synovial MSCs with 2-step surgery could promote articular cartilage regeneration in microminipig osteochondral defects. Study Design: Controlled laboratory study. Methods: Synovial MSCs derived from a microminipig were examined for in vitro colony-forming and multidifferentiation abilities. An aggregate of 250,000 synovial MSCs was formed with hanging drop culture, and 16 aggregates (for each defect) were implanted on both osteochondral defects (6 × 6 × 1.5 mm) created in the medial femoral condyle and femoral groove (MSC group). The defects in the contralateral knee were left empty (control group). The knee joints were evaluated at 4 and 12 weeks by macroscopic findings and histology. MRI T1rho mapping images were acquired at 12 weeks. For cell tracking, synovial MSCs were labeled with ferucarbotran before aggregate formation and were observed with MRI at 1 week. Results: Synovial MSCs showed in vitro colony-forming and multidifferentiation abilities. Regenerative cartilage formation was significantly better in the MSC group than in the control group, as indicated by International Cartilage Repair Society score (macro), modified Wakitani score (histology), and T1rho mapping (biochemical MRI) in the medial condyle at 12 weeks. Implanted cells, labeled with ferucarbotran, were observed in the osteochondral defects at 1 week with MRI. No significant difference was noted in the modified Wakitani score at 4 weeks in the medial condyle and at 4 and 12 weeks in the femoral groove. Conclusion: Transplantation of autologous synovial MSC aggregates promoted articular cartilage regeneration at the medial femoral condyle at 12 weeks in microminipigs. Clinical Relevance: Aggregates of autologous synovial MSCs could expand the indications for cartilage repair with synovial MSCs.

Zonal variations of the T1 rho value were observed in intact menisci due to varying structure in each zone. T1 rho values were correlated with histological changes such as collagen fiber organization and safranin-o stainability in incised menisci. This study supports T1 rho mapping as useful for evaluating ultrastructural composition in menisci.