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

间充质干细胞(MSCs)具有向间充质组织分化的潜能。本研究的目的是阐明MSC_1软骨再生的详细过程。我们研究了滑膜来源的间充质干细胞与骨膜覆盖的胶原凝胶的复合材料在体内的软骨形成。(1)骨髓、滑膜和软骨组织来源的干细胞的比较。我们证明了滑膜来源的MSCs具有更强的体外软骨形成能力。软骨再生的最佳细胞来源。(2)骨髓间充质干细胞/胶原凝胶复合材料的体外软骨形成。我们证明了滑膜来源的骨髓间充质干细胞/胶原凝胶复合材料具有更强的体外成软骨和成骨能力。(3)移植。4周后，尽管细胞密度下降，但移植的MSCs仍能广泛生成大量的软骨基质。骨膜变薄，骨膜中的软骨前体细胞产生少量的软骨基质。在深层，移植的MSCs向肥大的软骨细胞发展。在深部，部分移植细胞分化为骨细胞，髓腔周围细胞被宿主细胞取代。在下一阶段，骨和软骨之间的边界发展到原来的高度。此外，天然软骨和再生软骨之间的整合也得到了改善。移植的滑膜来源的MSCs会随着微环境的不同而在一段时间内发生变化。我们的结果将推进基于MSC的软骨损伤治疗策略，并为控制MSCs多系分化的机制提供线索。

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.