|
1
|
Lei T, Deng S, Chen P, Xiao Z, Cai S, Hang Z, Yang Y, Zhang X, Li Q, Du H. Metformin enhances the osteogenesis and angiogenesis of human umbilical cord mesenchymal stem cells for tissue regeneration engineering. Int J Biochem Cell Biol 2021; 141:106086. [PMID: 34551339 DOI: 10.1016/j.biocel.2021.106086] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 09/13/2021] [Accepted: 09/16/2021] [Indexed: 12/18/2022]
Abstract
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.
Collapse
Affiliation(s)
- Tong Lei
- 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
| | - Shiwen Deng
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
| | - Peng Chen
- Robot Intelligent Laboratory of Traditional Chinese Medicine, Experimental Research Center, China Academy of Chinese Medical Sciences & MEGAROBO, Dongcheng District, Beijing 100700, China
| | - Zhuangzhuang Xiao
- 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
| | - Shanglin Cai
- 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
| | - Zhongci Hang
- 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
| | - Yanjie Yang
- 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
| | - Xiaoshuang Zhang
- 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
| | - Quanhai Li
- 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.
| | - Hongwu Du
- 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.
| |
Collapse
|
|
2
|
Jiang LL, Liu L. Effect of metformin on stem cells: Molecular mechanism and clinical prospect. World J Stem Cells 2020; 12:1455-1473. [PMID: 33505595 PMCID: PMC7789120 DOI: 10.4252/wjsc.v12.i12.1455] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 09/28/2020] [Accepted: 10/23/2020] [Indexed: 02/06/2023] Open
Abstract
Metformin is a first-line medication for type II diabetes. Numerous studies have shown that metformin not only has hypoglycemic effects, but also modulates many physiological and pathological processes ranging from aging and cancer to fracture healing. During these different physiological activities and pathological changes, stem cells usually play a core role. Thus, many studies have investigated the effects of metformin on stem cells. Metformin affects cell differentiation and has promising applications in stem cell medicine. It exerts anti-aging effects and can be applied to gerontology and regenerative medicine. The potential anti-cancer stem cell effect of metformin indicates that it can be an adjuvant therapy for cancers. Furthermore, metformin has beneficial effects against many other diseases including cardiovascular and autoimmune diseases. In this review, we summarize the effects of metformin on stem cells and provide an overview of its molecular mechanisms and clinical prospects.
Collapse
Affiliation(s)
- Lin-Li Jiang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lei Liu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China.
| |
Collapse
|