Abstract
Hypoxia treatment enhances paracrine effect of mesenchymal stem cells (MSCs). The aim of this study was to investigate whether exosomes from hypoxia-treated MSCs (Exo H ) are superior to those from normoxia-treated MSCs (Exo N ) for myocardial repair. Mouse bone marrow-derived MSCs were cultured under hypoxia or normoxia for 24 h, and exosomes from conditioned media were intramyocardially injected into infarcted heart of C57BL/6 mouse. Exo H resulted in significantly higher survival, smaller scar size and better cardiac functions recovery. Exo H conferred increased vascular density, lower cardiomyocytes (CMs) apoptosis, reduced fibrosis and increased recruitment of cardiac progenitor cells in the infarcted heart relative to Exo N . MicroRNA analysis revealed significantly higher levels of microRNA-210 (miR-210) in Exo H compared with Exo N . Transfection of a miR-210 mimic into endothelial cells (ECs) and CMs conferred similar biological effects as Exo H . Hypoxia treatment of MSCs increased the expression of neutral sphingomyelinase 2 (nSMase2) which is crucial for exosome secretion. Blocking the activity of nSMase2 resulted in reduced miR-210 secretion and abrogated the beneficial effects of Exo H . In conclusion, hypoxic culture augments miR-210 and nSMase2 activities in MSCs and their secreted exosomes, and this is responsible at least in part for the enhanced cardioprotective actions of exosomes derived from hypoxia-treated cells.
Original language | English (US) |
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Pages (from-to) | 1659-1670 |
Number of pages | 12 |
Journal | Artificial Cells, Nanomedicine and Biotechnology |
Volume | 46 |
Issue number | 8 |
DOIs | |
State | Published - Nov 17 2018 |
Keywords
- Exosomes
- MSCs
- hypoxia
- microRNA210
- myocardial infarction
- nSMase2
ASJC Scopus subject areas
- Biotechnology
- Medicine (miscellaneous)
- Biomedical Engineering
- Pharmaceutical Science