间充质干细胞
滑液
血小板源性生长因子受体
滑膜
干细胞
体外
免疫学
细胞生物学
化学
医学
病理
骨关节炎
生长因子
生物
关节炎
内科学
受体
替代医学
生物化学
作者
Kentaro Endo,Kiyotaka Horiuchi,Hisako Katano,Nobutake Ozeki,Yuriko Sakamaki,Hideyuki Koga,Ichiro Sekiya
标识
DOI:10.1007/s12015-021-10156-4
摘要
Drugs that can induce mesenchymal stem cell (MSC) mobilization from synovium into synovial fluid will enable regenerative medicine in joints without use of exogenous MSCs. An in vitro synovial MSC migration model had previously been developed for screening but had problems in practical application. We herein developed a novel in vitro model, explored cytokines for synovial MSC mobilization with this model, and verified whether MSCs in synovial fluid increase following intra-articular injection of the cytokine.Human synovial MSCs embedded in a mixture of Matrigel and type 1 collagen hydrogel were placed on a culture insert and then put in medium containing migration factor. Of the six cytokines, we identified the one that mobilizes the highest number of MSCs. PDGF-BB or PBS was injected into rat knees, and 48 h later, synovial fluid was collected and cultured. The cells were examined for MSC properties.PDGF-BB was the most effective for synovial MSC mobilization among six cytokines. The effect of PDGF-BB was inhibited by a PRGFR inhibitor. Injection of PDGF-BB into rat knees increased colony-forming cells in the synovial fluid. These cells had surface epitopes and multipotency comparable to MSCs and a higher capacity for proliferation, colony formation, and chondrogenesis.This novel in vitro model recapitulated the migration of MSCs from synovium into synovial fluid. Our exploration of cytokines revealed that PDGF-BB strongly induced in vitro synovial MSC migration, while intra-articular injection of PDGF-BB increased in vivo MSC numbers in synovial fluid in rats.
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