In vivo chondrogenesis by applying composites of synovium-derived mesenchymal stem cells with collagen gel covered with periosteum.

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Mesenchymal stem cells (MSCs) have the potential to differentiate into the lineages of mesenchymal tissues. The aim of this study is to clarify the detailed process of cartilage regeneration in MSC_s.We examined "In vivo chondrogenesis by applying composites of synovium-derived mesenchymal stem cells with collagen gel covered with periosteum" as follows.(1) Comparison of stem cells derived from bone marrow, synovium and cartilage tissue.We demonstrated that synovium-derived MSCs had greater in vitro chondrogenic ability, suggesting an optimal cell source for cartilage regeneration.(2) In vitro cartilage formation of composites of MSCs with collagen gel.We demonstrated that the composites of synovium-derived MSCs with collagen gel had greater in vitro chondrogenic and osteogenic ability.(3) Transplantation.We transplanted composites of MSCs with collagen gel into a full-thickness articular cartilage defect of adult rabbits. After 4 weeks, although the cell density decreased, transplanted MSCs produced a great amount of cartilage matrix extensively. The periosteum became thinner and chondroprogenitors in the periosteum produced a small amount of cartilage matrix. In the deeper zone, transplanted MSCs progressed to the hypertrophic chondrocytes. In the deep zone, some transplanted cells differentiated into bone cells and cells around medullary cavity were replaced with host cells. In the next phase, border between bone and cartilage progressed to the original height. Also, integrations between native and regenerated cartilage were improved. Transplanted synovium-derived MSCs altered over a time course according to the micro environments. Our results will advance MSC-based therapeutic strategies for cartilage injury and provide the clues for the mechanisms that govern multilineage differentiation of MSCs.