Anti-hypertrophic effect of synovium-derived stromal cells on costal chondrocytes promotes cartilage repairs

Abstract

Background Costal chondrocytes (CCs), as a promising donor cell source for cell-based therapy for cartilage repair, have strong tendency of hypertrophy and calcification, which limited CCs from further application in cartilage regenerative medicine. Synovium-derived stromal cells (SDSCs), have shown their beneficial effect for chondrocytes to maintain phenotype. This study aims to investigate whether SDSCs could help CCs to maintain chondrogenic phenotype and suppress hypertrophic differentiation in cartilage repairs. Methods CCs were directly cocultured with SDSCs in pellet or indirectly cocultured using a conditioned medium in vitro for 3 weeks. Cartilage matrix formation and hypertrophic differentiation of CCs were analyzed by RT-PCR, biochemical assays, and histological staining. Cocultured pellets were implanted into the osteochondral defects made on the femoral groove of the rats. Then, macroscopic and histological evaluations were performed. Results Pellets formed by CCs alone and CCs cocultured with SDSCs reveal equal cartilage matrix deposition. However, the gene expression of type X collagen was significantly downregulated in cocultured pellets. Immunohistochemistry analysis revealed suppressed expression of type X collagen in cocultured pellets, indicating SDSCs may suppress hypertrophic differentiation of chondrocytes. Further in indirect coculture experiment, SDSCs suppressed type X collagen expression as well and promoted the proliferation of CCs, indicating SDSCs may influence CCs by paracrine mechanism. The pellets implanted in the osteochondral defects showed good restoration effects, whereas the grafts constructed with CCs and SDSCs showed lower type X expression levels. Conclusion These results suggest that SDSCs may maintain the phenotype of CCs and prevent the hypertrophic differentiation of CCs in cartilage repair. The Translational Potential of this Article : CCs is a promising donor cell source for cell-based therapy for cartilage repair. Based on our study, cocultured with SDSCs weakened the tendency of hypertrophy and calcification of CCs, which provide a potential usage of SDSCs in CCs-based cartilage repair therapy to suppress newly formed cartilage calcification and improve clinical outcomes.

Co-culture pellet of human Wharton’s jelly mesenchymal stem cells and rat costal chondrocytes as a candidate for articular cartilage regeneration: in vitro and in vivo study

“…There was no significant difference in hypertrophic gene expression. These findings are consistent with those of our previous and some other studies, indicating that MSCs can stimulate chondrogenesis due to trophic effects on chondrocytes [ 50 – 53 , 55 – 57 ]. However, the chondrogenic promotion and anti-hypertrophic effects of CCs on hWJMSCs were not significant.…”

Natural polymer‐based adhesive hydrogel for biomedical applications

“…Furthermore, cartilage defects lack a regenerative capacity, as they lack blood vessels/ neural tubes [214,[226][227][228]. Tissue engineering based on biological scaffold seed cells and favourable growth factors is the most promising strategy for cartilage tissue repair [229]. After subcutaneous implantation, chondrocytes, MSCs, and embryonic stem cells can be wrapped in a hydrogel that eventually forms a chondro-like tissue.…”

Functionalized Hydrogels for Cartilage Repair: The Value of Secretome-Instructive Signaling

“…As in many adult tissues, MSCs were also isolated from the synovial membrane (SM-MSCs) [ 52 ]. Indirect co-culture of these cells and costal chondrocytes (CCs) showed that CM produced by SM-MSCs induced proliferation of CCs and a decrease in type X collagen (COLX) expression, suggesting that paracrine factors from SM-MSCs could participate in the anti-hypertrophic effect induced by these cells [ 53 ].…”