Transplantation of Aggregates of Autologous Synovial Mesenchymal Stem Cells for Treatment of Cartilage Defects in the Femoral Condyle and the Femoral Groove in Microminipigs

Abstract

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.

Exosomes: roles and therapeutic potential in osteoarthritis

“…195 Intra-articular injection of SMSCs could markedly promote cartilage repair and be used to treat joint-related diseases, including OA, in experimental animal models. [196][197][198][199] Recently, several studies revealed that exosomes derived from SMSCs could effectively promote cartilage regeneration and attenuate OA progression. 122,195,200 Tao et al reported that SMSC-derived exosomes could induce the proliferation and emigration of articular chondrocytes in a Wnt5a/Wnt5b/YAPdependent manner.…”

Synovial membrane mesenchymal stem cells: past life, current situation, and application in bone and joint diseases

“…Nakamura et al [75] injected fluorescently labeled allogeneic SM-MSCs suspension into the osteochondral defect in pigs; 4 weeks later, they found the osteochondral defect was filled with cartilage matrix. Kondo et al [76] selected autologous SM-MSCs aggregates to investigate whether SM-MSCs could successfully repair the cartilage defects in microminipigs in the medial femoral condyle and femoral groove. Their results showed that the transplantation of SM-MSC aggregates promoted the regeneration of the articular cartilage in the medial femoral condyle of microminipig but not in the femoral groove, suggesting that the site of cartilage defect may also affect the cartilage repair ability of stem cells.…”

Cell Interplay in Osteoarthritis

“…Studies have shown that SMSCs from OA patients can repair cartilage through allogenic tissue-engineered constructs in both in vitro and in vivo models. In experimental animal models, the injection of SMSCs into the joint cavity achieved a similar effect (Kondo et al, 2019;Enomoto et al, 2020;Dragoo et al, 2012). Infrapatellar fat pad (IPFP), a column of fat tissue located behind the patella, and synovium are involved in the occurrence and development of intra-articular diseases, such as OA (Favero et al, 2017).…”