miR-10a rejuvenates aged human mesenchymal stem cells and improves heart function after myocardial infarction through KLF4

miR-10a rejuvenates aged human mesenchymal stem cells and improves heart function after myocardial infarction through KLF4

Aging is one of the key factors that regulate the function of human bone marrow mesenchymal stem cells (hBM-MSCs) and related changes in microRNA (miRNA) expression. However, data reported on aging-related miRNA changes in hBM-MSCs are limited. We demonstrated previously that miR-10a is significantl...

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Bibliographic Details
Published in:Stem cell research & therapy Vol. 9; no. 1; p. 151
Main Authors: Dong, Jun, Zhang, Zhenhui, Huang, Hongshen, Mo, Pei, Cheng, Chuanfan, Liu, Jianwei, Huang, Weizhao, Tian, Chaowei, Zhang, Chongyu, Li, Jiao
Format: Journal Article
Language:English
Published: England BioMed Central Ltd 30-05-2018
BioMed Central
BMC
Subjects:
Aging
AKT protein
Analysis
Angiogenesis
Antisense DNA
Apoptosis
Bone marrow
Care and treatment
Cell growth
Cell survival
Chemotherapy
Heart
Heart attack
Heart attacks
Hypoxia
Ischemia
Kinases
KLF4 protein
Leukemia
Mesenchymal stem cells
Mesenchyme
MicroRNA
MicroRNAs
miRNA
Myocardial infarction
Neuroblastoma
Paracrine signalling
Rejuvenation
Senescence
Stem cell research
Stem cell transplantation
Stem cells
Studies
Transplantation
Vascular endothelial growth factor
China
Myocardial infarction
Aging
MicroRNA
Rejuvenation
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Summary:Aging is one of the key factors that regulate the function of human bone marrow mesenchymal stem cells (hBM-MSCs) and related changes in microRNA (miRNA) expression. However, data reported on aging-related miRNA changes in hBM-MSCs are limited. We demonstrated previously that miR-10a is significantly decreased in aged hBM-MSCs and restoration of the miR-10a level attenuated cell senescence and increased the differentiation capacity of aged hBM-MSCs by repressing Krüpple-like factor 4 (KLF4). In the present study, miR-10a was overexpressed or KLF4 was downregulated in old hBM-MSCs by lentiviral transduction. The hypoxia-induced apoptosis, cell survival, and cell paracrine function of aged hBM-MSCs were investigated in vitro. In vivo, miR-10a-overexpressed or KLF4-downregulated old hBM-MSCs were implanted into infarcted mouse hearts after myocardial infarction (MI). The mouse cardiac function of cardiac angiogenesis was measured and cell survival of aged hBM-MSCs was investigated. Through lentivirus-mediated upregulation of miR-10a and downregulation of KLF4 in aged hBM-MSCs in vitro, we revealed that miR-10a decreased hypoxia-induced cell apoptosis and increased cell survival of aged hBM-MSCs by repressing the KLF4-BAX/BCL2 pathway. In vivo, transplantation of miR-10a-overexpressed aged hBM-MSCs promoted implanted stem cell survival and improved cardiac function after MI. Mechanistic studies revealed that overexpression of miR-10a in aged hBM-MSCs activated Akt and stimulated the expression of angiogenic factors, thus increasing angiogenesis in ischemic mouse hearts. miR-10a rejuvenated aged hBM-MSCs which improved angiogenesis and cardiac function in injured mouse hearts.
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ISSN:1757-6512
1757-6512
DOI:10.1186/s13287-018-0895-0