Optimal H2O2 preconditioning to improve BMSCs’ engraftment  in wounds healing

Abstract Background. The transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising therapeutic strategy for wound healing. However, the poor migration capacity and low survival rate of transplanted BMSCs in wounds weaken their potential application. Objective. The optimal protocol for BMSCs preconditioned with H2O2 was investigated, and the therapeutic efficacy of preconditioned BMSCs in wounds was evaluated. Methods. Mouse BMSCs were exposed to various concentrations of H2O2, and their functions were assessed; The H2O2-preconditioned BMSCs were transplanted into mice with full-thickness excisional wounds. Wound analysis was performed to assess the transplantation efficacy. Results. Treatment BMSCs with 50 µM H2O2 for 12 h could enhance their proliferation, migration and survival by maximizing up-regulation the cyclin D1, SDF-1 and its receptors CXCR4/7 expressions, and activating the PI3K/Akt/mTOR pathway, but inhibiting the expression of p16 and GSK-3β. Meanwhile, oxidative stress-induced-BMSCs apoptosis was significantly attenuated by an obviously decreased ratio of Bax/Bcl-2 and cleaved caspase-9/3 expression. After transplantation of BMSCs, the migration of H2O2 preconditioned-BMSCs into the wounds was dramatically increased compared to un-preconditioned-BMSCs, and had an increased microvessel density and wound closure speed. Conclusions. The findings suggested that 50 µM H2O2 pretreated for 12 h is the optimal precondition for the transplantation of BMSC, which gives a considerable insight that this protocol may be served as a promising candidate for improving the therapeutic potential of BMSCs for wound healing.