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Stem Cell Res Ther. 2018 May 30;9(1):151. doi: 10.1186/s13287-018-0895-0.

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

Author information

1
Guangzhou Institute of Cardiovascular Disease, Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.
2
Department of Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
3
Department of Intensive Care Unit, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
4
Toronto General Research Institute, University Health Network, Toronto, Canada.
5
Guangzhou Institute of Cardiovascular Disease, Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China. gzlijiao@163.com.
6
Toronto General Research Institute, University Health Network, Toronto, Canada. gzlijiao@163.com.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

miR-10a rejuvenated aged hBM-MSCs which improved angiogenesis and cardiac function in injured mouse hearts.

KEYWORDS:

Aging; MicroRNA; Myocardial infarction; Rejuvenation

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