Intra‐articular Injection of PDGF-BB Explored in a Novel in Vitro Model Mobilizes Mesenchymal Stem Cells From the Synovium Into Synovial Fluid in Rats

• Published in: Stem cell reviews and reports 2021-10, Vol.17 (5), p.1768-1779
• Main Authors: Endo, Kentaro, Horiuchi, Kiyotaka, Katano, Hisako, Ozeki, Nobutake, Sakamaki, Yuriko, Koga, Hideyuki, Sekiya, Ichiro
• Format: Article
• Language: English
• Subjects: Animals; Becaplermin; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Cell Biology; Cell culture; Chondrogenesis; Collagen; Colonies; Colony-forming cells; Cytokines; Epitopes; Hydrogels; Injection; Injections, Intra-Articular; Knee; Life Sciences; Mesenchymal Stem Cells; Platelet-derived growth factor; Platelet-derived growth factor BB; Rats; Regenerative medicine; Regenerative Medicine/Tissue Engineering; Stem cell transplantation; Stem Cells; Synovial Fluid; Synovium
• ISSN: 2629-3269; 2629-3277
• DOI: 10.1007/s12015-021-10156-4

Background 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. Methods 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. Results 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. Conclusions 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.