Optimal H2O2 preconditioning to improve bone marrow mesenchymal stem cells’ engraftment in wound healing

Stem Cell Research & Therapy

Hong Huang¹  Ling Guo¹  Hua-cai Zhang¹  Di Liu¹  Shu Zhang¹  Min-jia Chen¹  Ling Zeng¹  Jun-wei Mi¹  Juan Du¹  Jian-hui Sun¹  Anqiang Zhang¹  Dan-feng Yuan¹  Da-lin Wen¹  Ya Zhang¹  Ya-lei Ning¹  Jianxin Jiang¹ 

[1] State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, 400042, Chongqing, China;

关键词: Mesenchymal stem cells;    Hydrogen peroxide;    Preconditioning;    Oxidative stress;    Wound healing;   

DOI  :  10.1186/s13287-020-01910-5

来源: Springer

【 摘 要 】

BackgroundThe 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.ObjectiveTo identify the optimal protocol for BMSCs preconditioned with H2O2 and improve the therapeutic efficacy using H2O2-preconditioned BMSCs in wound healing.MethodsMouse BMSCs were exposed to various concentrations of H2O2, and the key cellular functional properties were assessed to determine the optimal precondition with H2O2. The H2O2-preconditioned BMSCs were transplanted into mice with full-thickness excisional wounds to evaluate their healing capacity and tissue engraftment.ResultsTreatment BMSCs with 50 μM H2O2 for 12 h could significantly enhance their proliferation, migration, and survival by maximizing the upregulation of 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 BMSC apoptosis was also significantly attenuated by the same protocol pretreatment with a decreased ratio of Bax/Bcl-2 and cleaved caspase-9/3 expression. Moreover, after the identification of the optimal protocol of H2O2 precondition in vitro, the migration and tissue engraftment of transfused BMSCs with H2O2 preconditioning were dramatically increased into the wound site as compared to the un-preconditioned BMSCs. The increased microvessel density and the speedy closure of the wounds were observed after the transfusion of H2O2-preconditioned BMSCs.ConclusionsThe findings suggested that 50 μM H2O2 pretreated for 12 h is the optimal precondition for the transplantation of BMSCs, 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.

【 授权许可】

CC BY