Journal
STEM CELL RESEARCH & THERAPY
Volume 9, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13287-018-0895-0
Keywords
Aging; MicroRNA; Rejuvenation; Myocardial infarction
Funding
- National Natural Science Foundation of China [81602334, 81401156]
- Science and Technology Planning Project of Guangdong Province, China [2016A020215166, 2017A020215084]
- Natural Science Foundation of Guangdong Province, China [2016A030310285]
- Educational Commission of Guangdong Province, China [2015KQNCX125, 2016KTSCX113, 2016KQNCX130]
- Bureau of Education of Guangzhou Municipality, China [1201581618]
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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 Kruppie-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 lenti-virus-mediated upregulation of miR-10a and down regulation of KLF4 in aged hBM-MSCs in vitro, we levealed 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.
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