Metformin promotes angiogenesis by enhancing VEGFa secretion by adipose-derived stem cells via the autophagy pathway

Author:

Tao Zihan1,Liu Lei1,Wu Minliang1,Wang Qianqian2,Wang Yuchong13,Xiong Jiachao4,Xue Chunyu1

Affiliation:

1. Department of Plastic Surgery, Changhai Hospital, Naval Medical University , Shanghai, China

2. Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Center, Naval Medical University , Shanghai, China

3. School of Life Sciences and Technology, Tongji University , Shanghai, China

4. Department of Plastic and Reconstructive Surgery, School of Medicine, Shanghai East Hospital, Tongji University , Shanghai, China

Abstract

Abstract Human adipose tissue-derived stem cell (ADSC) derivatives are cell-free, with low immunogenicity and no potential tumourigenicity, making them ideal for aiding wound healing. However, variable quality has impeded their clinical application. Metformin (MET) is a 5′ adenosine monophosphate-activated protein kinase activator associated with autophagic activation. In this study, we assessed the potential applicability and underlying mechanisms of MET-treated ADSC derivatives in enhancing angiogenesis. We employed various scientific techniques to evaluate the influence of MET on ADSC, assess angiogenesis and autophagy in MET-treated ADSC in vitro, and examine whether MET-treated ADSC increase angiogenesis. We found that low MET concentrations exerted no appreciable effect on ADSC proliferation. However, MET was observed to enhance the angiogenic capacity and autophagy of ADSC. MET-induced autophagy was associated with increased vascular endothelial growth factor A production and release, which contributed to promoting the therapeutic efficacy of ADSC. In vivo experiments confirmed that in contrast to untreated ADSC, MET-treated ADSC promoted angiogenesis. Our findings thus indicate that the application of MET-treated ADSC would be an effective approach to accelerate wound healing by promoting angiogenesis at wound sites.

Funder

National Natural Science Foundation of China

Naval Military Medical University Basic Research Project

Publisher

Oxford University Press (OUP)

Subject

Biomaterials

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