Stem Cell Research & Therapy (Mar 2022)

Ascorbic acid 2-glucoside preconditioning enhances the ability of bone marrow mesenchymal stem cells in promoting wound healing

  • Yi Yi,
  • Min Wu,
  • Xiaomei Zhou,
  • Mingchen Xiong,
  • Yufang Tan,
  • Honghao Yu,
  • Zeming Liu,
  • Yiping Wu,
  • Qi Zhang

DOI
https://doi.org/10.1186/s13287-022-02797-0
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 17

Abstract

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Abstract Background Nowadays, wound is associated with a complicated repairing process and still represents a significant biomedical burden worldwide. Bone marrow mesenchymal stem cells (BMSCs) possess multidirectional differentiation potential and secretory function, emerging as potential cellular candidates in treating wounds. Ascorbic acid 2-glucoside (AA2G) is a well-known antioxidant and its function in BMSC-promoting wound healing is worth exploring. Methods The in vitro cell proliferation, migration, and angiogenesis of BMSCs and AA2G-treated BMSCs were detected by flow cytometry, EDU staining, scratch assay, transwell assay, and immunofluorescence (IF). Besides, the collagen formation effect of AA2G-treated BMSCs conditioned medium (CM) on NIH-3T3 cells was evaluated by hydroxyproline, qRT-PCR and IF staining detection. Next, in the wound healing mouse model, the histological evaluation of wound tissue in PBS, BMSCs, and AA2G-treated BMSCs group were further investigated. Lastly, western blot and ELISA were used to detect the expression levels of 5-hmc, TET2 and VEGF protein, and PI3K/AKT pathway activation in BMSCs treated with or without AA2G. Results The in vitro results indicated that AA2G-treated BMSCs exhibited stronger proliferation and improved the angiogenesis ability of vascular endothelial cells. In addition, the AA2G-treated BMSCs CM enhanced migration and collagen formation of NIH-3T3 cells. In vivo, the AA2G-treated BMSCs group had a faster wound healing rate and a higher degree of vascularization in the new wound, compared with the PBS and BMSCs group. Moreover, AA2G preconditioning might enhance the demethylation process of BMSCs by regulating TET2 and up-regulating VEGF expression by activating the PI3K/AKT pathway. Conclusions AA2G-treated BMSCs promoted wound healing by promoting angiogenesis and collagen deposition, thereby providing a feasible strategy to reinforce the biofunctionability of BMSCs in treating wounds.

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