Reparative homing of bone mesenchymal stem cells induced by iMSCs via the SDF-1/CXCR4 axis for articular cartilage defect restoration
Gang Cheng, Xulei Wang, Feng Zhang, Kang Wang, Minghao Yin, Tingting Guo, Nuo Xu, Wei Wei, Shangxue Yan
Abstract
BACKGROUND: The intrinsic healing ability of articular cartilage is poor after injury or illness, and untreated injury could lead to cartilage degeneration and ultimately osteoarthritis. iMSCs are derived from embryonic induced pluripotent stem cells and have strong therapeutic capabilities in the repair of cartilage defects, while the mechanism of action is unclear. The aim of this study is to clarify the repair mode of iMSCs on cartilage defects in rat knee joints, elucidate the chemotactic effect of iMSCs on autologous BMSCs in rats, and provide a basis for the treatment of cartilage defects and endogenous regeneration with iMSCs. METHODS: Based on the establishment of the rat cartilage defect model, the reparative effect of iMSCs on the rat cartilage defect was evaluated. The cartilage repair was evaluated by quantitative score, H&E staining, Masson staining and Safranin-O staining, and the metabolic changes of iMSCs in the joint cavity were detected in vivo. The expression of SOX9, CD29, CD90, ColⅠ, ColⅡ, PCNA, SDF-1, and CXCR4 was detected by immunohistochemistry (IHC), IF, flow cytometry, respectively. After co-culturing iMSCs with BMSCs in vitro, the expression of CXCR4/SDF-1 on the cell membrane surface of BMSCs was detected by western blotting.; The level of p-Akt and p-Erk1/2 in total protein of BMSCs were detected by western blotting. SIGNIFICANCE: Our research results provide experimental evidence for the treatment of cartilage defects and endogenous regeneration with iMSCs; This also provides new ideas for the clinical treatment of cartilage defects using iMSCs.