Synovial Stem Cells Are Regionally Specified According to Local Microenvironments After Implantation for Cartilage Regeneration

Abstract

We previously demonstrated that synovium-derived MSCs had greater in vitro chondrogenic ability than other mesenchymal tissues, suggesting a superior cell source for cartilage regeneration. Here, we transplanted undifferentiated synovium-derived MSCs into a full-thickness articular cartilage defect of adult rabbits and defined the cellular events to elucidate the mechanisms that govern multilineage differentiation of MSCs. Full-thickness osteochondral defects were created in the knee; the defects were filled with 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate-labeled MSCs and covered with periosteum. 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 chondrocyte-like cells. In the deep zone, some transplanted cells differentiated into bone cells and were replaced with host cells thereafter. In the next phase, the border between bone and cartilage moved upwards. In addition, integrations between native cartilage and regenerated tissue were improved. Chondrocyte-like cells derived from the transplanted MSCs still remained at least after 24 weeks. Histological scores of the MSC group improved continuously and were always better than those of two other control groups. Immunohistological analyses and transmission electron microscopy confirmed that the MSCs produced abundant cartilage matrix. We demonstrated that transplanted synovium-derived MSCs were altered over a time course according to the microenvironments. Our results will advance MSC-based therapeutic strategies for cartilage injury and provide the clues for the mechanisms that govern multilineage differentiation of MSCs. STEM CELLS 2007;25:689 -696

Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts

“…8 Furthermore, synovial MSCs were shown capable of rabbit cartilage repair. 9 These results indicated that synovium represents a precious source of MSCs, and also opened new approaches for combating synovial inflammation, by interfering with signaling pathways involved in MSC differentiation.…”

Morphological differences during in vitro chondrogenesis of bone marrow-, synovium-MSCs, and chondrocytes

“…[1][2][3][4] MSCs can be obtained from a variety of mesenchymal tissues including bone marrow, 5 which seems to be the most popular MSC source at present. Synovium, a thin membrane covering the inside of joints, is another promising MSC source due to its high chondrogenic potential.…”

The influence of sex on the chondrogenic potential of muscle‐derived stem cells: Implications for cartilage regeneration and repair

“…For cartilage regeneration and repair, stem cells are an attractive cell source due to their superior capacity for self-renewal, proliferation, and response to stress (11,12). Results of several studies have suggested that various stem cells have potential for cartilage regeneration and repair in experimental cartilage injury models (13)(14)(15). Recently, autologous stem cell-based tissue engineering has been used clinically for cartilage repair and regeneration (16,17).…”