PMID- 34551339
OWN - NLM
STAT- MEDLINE
DCOM- 20211216
LR  - 20211216
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Linking)
VI  - 141
DP  - 2021 Dec
TI  - Metformin enhances the osteogenesis and angiogenesis of human umbilical cord 
      mesenchymal stem cells for tissue regeneration engineering.
PG  - 106086
LID - S1357-2725(21)00167-9 [pii]
LID - 10.1016/j.biocel.2021.106086 [doi]
AB  - 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 PPARgamma 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.
CI  - Copyright (c) 2021. Published by Elsevier Ltd.
FAU - Lei, Tong
AU  - Lei T
AD  - Daxing Research Institute, University of Science and Technology Beijing. Beijing 
      100083, China; School of Chemistry and Biological Engineering, University of 
      Science and Technology Beijing, Beijing 100083, China.
FAU - Deng, Shiwen
AU  - Deng S
AD  - School of Chemistry and Biological Engineering, University of Science and 
      Technology Beijing, Beijing 100083, China.
FAU - Chen, Peng
AU  - Chen P
AD  - Robot Intelligent Laboratory of Traditional Chinese Medicine, Experimental 
      Research Center, China Academy of Chinese Medical Sciences & MEGAROBO, Dongcheng 
      District, Beijing 100700, China.
FAU - Xiao, Zhuangzhuang
AU  - Xiao Z
AD  - Daxing Research Institute, University of Science and Technology Beijing. Beijing 
      100083, China; School of Chemistry and Biological Engineering, University of 
      Science and Technology Beijing, Beijing 100083, China.
FAU - Cai, Shanglin
AU  - Cai S
AD  - Daxing Research Institute, University of Science and Technology Beijing. Beijing 
      100083, China; School of Chemistry and Biological Engineering, University of 
      Science and Technology Beijing, Beijing 100083, China.
FAU - Hang, Zhongci
AU  - Hang Z
AD  - Daxing Research Institute, University of Science and Technology Beijing. Beijing 
      100083, China; School of Chemistry and Biological Engineering, University of 
      Science and Technology Beijing, Beijing 100083, China.
FAU - Yang, Yanjie
AU  - Yang Y
AD  - Daxing Research Institute, University of Science and Technology Beijing. Beijing 
      100083, China; School of Chemistry and Biological Engineering, University of 
      Science and Technology Beijing, Beijing 100083, China.
FAU - Zhang, Xiaoshuang
AU  - Zhang X
AD  - Daxing Research Institute, University of Science and Technology Beijing. Beijing 
      100083, China; School of Chemistry and Biological Engineering, University of 
      Science and Technology Beijing, Beijing 100083, China.
FAU - Li, Quanhai
AU  - Li Q
AD  - Cell Therapy Laboratory, the First Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei 050031, China; Department of Immunology, Basic Medical 
      College, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic 
      address: liquanh2@163.com.
FAU - Du, Hongwu
AU  - Du H
AD  - Daxing Research Institute, University of Science and Technology Beijing. Beijing 
      100083, China; School of Chemistry and Biological Engineering, University of 
      Science and Technology Beijing, Beijing 100083, China. Electronic address: 
      hongwudu@ustb.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210920
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Cell Differentiation
MH  - Humans
MH  - Mesenchymal Stem Cells
MH  - Metformin
MH  - *Osteogenesis
MH  - *Tissue Engineering
OTO - NOTNLM
OT  - Angiogenesis
OT  - Metformin
OT  - Osteogenesis
OT  - Proteomics
OT  - hUC-MSCs
EDAT- 2021/09/23 06:00
MHDA- 2021/12/17 06:00
CRDT- 2021/09/22 20:08
PHST- 2021/08/04 00:00 [received]
PHST- 2021/09/13 00:00 [revised]
PHST- 2021/09/16 00:00 [accepted]
PHST- 2021/09/23 06:00 [pubmed]
PHST- 2021/12/17 06:00 [medline]
PHST- 2021/09/22 20:08 [entrez]
AID - S1357-2725(21)00167-9 [pii]
AID - 10.1016/j.biocel.2021.106086 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2021 Dec;141:106086. doi: 10.1016/j.biocel.2021.106086. 
      Epub 2021 Sep 20.