Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, 23 You Zheng Street, Nangang District, Harbin 150001, China.
Microscopic Hand Surgery, People's Hospital of Hainan Province, Haikou 570100, China.
Stem Cells Int. 2014;2014:125683. doi: 10.1155/2014/125683. Epub 2014 Dec 3.
Coculture of mesenchymal stem cells with chondrocytes increases production of cartilaginous matrix. Chondrocytes isolated from late stage osteoarthritic patients usually lost their phenotype of producing cartilaginous matrix. Fibroblast growth factor 18 is believed to redifferentiate OA chondrocyte into functionally active chondrocytes. The aim of this study is to investigate the supportive effects of MSCs on OA chondrocytes and test if FGF18 could enhance the responsiveness of OA chondrocytes to the support of MSCs in a coculture system. Both pellet and transwell co-cultures were used. GAG quantification, hydroxyproline assay, and qPCR were performed. An ectopic models of cartilage formation was also applied. Our data indicated that, in pellets coculture of MSCs and OA chondrocytes, matrix production was increased in the presence of FGF18, comparing to the monoculture of chondrocytes. Results from transwell coculture study showed that expression of matrix producing genes in OA chondrocytes increased when cocultured with MSCs with FGF18 in culture medium, while hypertrophic genes were not changed by coculture. Finally, coimplantation of MSCs with OA chondrocytes produces more matrix than chondrocytes only. In conclusion, FGF18 can restore the responsiveness of OA chondrocytes to the trophic effects of MSCs. Coimplantation of MSCs and OA chondrocytes treated with FGF18 may be a good alternative cell source for regenerating cartilage tissue that is degraded during OA pathological changes.
骨髓间充质干细胞与软骨细胞共培养可增加软骨基质的产生。从晚期骨关节炎患者中分离的软骨细胞通常会失去产生软骨基质的表型。成纤维细胞生长因子 18 被认为可将 OA 软骨细胞重分化为具有功能活性的软骨细胞。本研究旨在探讨间充质干细胞对 OA 软骨细胞的支持作用，并测试 FGF18 是否可以增强 OA 软骨细胞在共培养系统中对间充质干细胞支持的反应性。我们使用了微球和 Transwell 共培养两种方法。进行了 GAG 定量、羟脯氨酸测定和 qPCR。还应用了软骨形成的异位模型。我们的数据表明，在 MSC 与 OA 软骨细胞的微球共培养中，与软骨细胞的单核培养相比，FGF18 的存在增加了基质的产生。Transwell 共培养研究的结果表明，当 OA 软骨细胞与 MSC 共培养时，培养基中存在 FGF18 可增加产生基质的基因的表达，而共培养不会改变肥大基因的表达。最后，与仅软骨细胞相比，MSC 与 OA 软骨细胞的共植入产生了更多的基质。总之，FGF18 可以恢复 OA 软骨细胞对 MSCs 营养作用的反应性。FGF18 处理的 MSC 和 OA 软骨细胞的共植入可能是一种替代细胞来源，可用于再生在 OA 病理变化过程中降解的软骨组织。
