Metformin enhances the osteogenesis and angiogenesis of human umbilical cord mesenchymal stem cells for tissue regeneration engineering

• Published in: The international journal of biochemistry & cell biology Vol. 141; p. 106086
• Main Authors: Lei, Tong, Deng, Shiwen, Chen, Peng, Xiao, Zhuangzhuang, Cai, Shanglin, Hang, Zhongci, Yang, Yanjie, Zhang, Xiaoshuang, Li, Quanhai, Du, Hongwu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.12.2021
• Subjects: adipogenesis; Adipogenesis - drug effects; Angiogenesis; bioinformatics; bone formation; cell cycle; Cell Differentiation - drug effects; cell movement; Cell Movement - drug effects; Cell Proliferation - drug effects; coculture; flow cytometry; gene expression regulation; gene ontology; hUC-MSCs; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; medicine; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Metformin; Metformin - pharmacology; Neovascularization, Physiologic - drug effects; Osteogenesis; Osteogenesis - drug effects; Proteomics; Tissue Engineering - methods; tissue repair; umbilical cord; Umbilical Cord - cytology; Umbilical Cord - drug effects; vascular endothelial growth factor receptor-2; DTT; ANG2; IAA; GO; DAVID; DMEM; Angiogenesis; hUC-MSCs; FBS; SCF; Proteomics; VEGFR; KEGG; TMT; Metformin; MSC; MET; RT-qPCR; Osteogenesis; DAPs
• ISSN: 1357-2725; 1878-5875; 1878-5875
• DOI: 10.1016/j.biocel.2021.106086

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a potential clinical material in regenerative medicine applications. Metformin has shown safety and effectiveness as a clinical drug. However, the effect of metformin as a treatment on hUC-MSCs is unclear. Our research aimed to explore the effects of metformin on the osteogenesis, adipogenesis and angiogenesis of hUC-MSCs, and attempted to explain the molecular fluctuations of metformin through the mapping of protein profiles. Proliferation assay, osteogenic and adipogenic differentiation induction, cell cycle, flow cytometry, quantitative proteomics techniques and bioinformatics analysis were used to detect the influences of metformin treatment on hUC-MSCs. Our results demonstrated that low concentrations of metformin promoted the proliferation of hUC-MSCs, but high concentrations of metformin inhibited it. Metformin exhibited promotion of osteogenesis but inhibition of adipogenesis. Metformin treated hUC-MSCs up-regulated the expression of osteogenic marker ALP, OCN and RUNX2, but down-regulated the expression of adipogenic markers PPARγ and LPL. Proteomics analysis found that up-regulation of differentially expressed proteins in metformin treatment group involved the biological process of cell migration in Gene Ontology analysis. Metformin enhanced cell migration of HUVEC in a co-culture system, and hUC-MSCs treated with metformin exhibited stronger angiogenesis in vitro and in vivo compared to the hUC-MSCs group. The results of RT-qPCR revealed that the SCF and VEGFR2 were raised in metformin treatment. This study can promote the application of hUC-MSCs treated with metformin to tissue engineering for vascular reconstruction and angiogenesis. [Display omitted] •Low concentrations of metformin promoted the proliferation of metformin while high concentrations inhibited it.•Metformin exhibited promotion of osteogenesis but inhibition of adipogenesis.•Metformin enhanced cell migration of HUVEC in co-culture system, and hUC-MSCs treated with metformin exhibited stronger angiogenesis in vitro and in vivo.