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) |
|---|---|
| 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 |
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Keywords
- Exosomes
- MSCs
- hypoxia
- microRNA210
- myocardial infarction
- nSMase2
ASJC Scopus subject areas
- Biotechnology
- Medicine (miscellaneous)
- Biomedical Engineering
- Pharmaceutical Science
Cite this
Myocardial reparative functions of exosomes from mesenchymal stem cells are enhanced by hypoxia treatment of the cells via transferring microRNA-210 in an nSMase2-dependent way. / Zhu, Jinyun; Lu, Kai; Zhang, Ning; Zhao, Yun; Ma, Qunchao; Shen, Jian; Lin, Yinuo; Xiang, Pingping; Tang, Yao Liang; Hu, Xinyang; Chen, Jinghai; Zhu, Wei; Webster, Keith A.; Wang, Jian’an; Yu, Hong.
In: Artificial Cells, Nanomedicine and Biotechnology, Vol. 46, No. 8, 17.11.2018, p. 1659-1670.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Myocardial reparative functions of exosomes from mesenchymal stem cells are enhanced by hypoxia treatment of the cells via transferring microRNA-210 in an nSMase2-dependent way
AU - Zhu, Jinyun
AU - Lu, Kai
AU - Zhang, Ning
AU - Zhao, Yun
AU - Ma, Qunchao
AU - Shen, Jian
AU - Lin, Yinuo
AU - Xiang, Pingping
AU - Tang, Yao Liang
AU - Hu, Xinyang
AU - Chen, Jinghai
AU - Zhu, Wei
AU - Webster, Keith A.
AU - Wang, Jian’an
AU - Yu, Hong
PY - 2018/11/17
Y1 - 2018/11/17
N2 - 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.
AB - 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.
KW - Exosomes
KW - MSCs
KW - hypoxia
KW - microRNA210
KW - myocardial infarction
KW - nSMase2
UR - http://www.scopus.com/inward/record.url?scp=85034211542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034211542&partnerID=8YFLogxK
U2 - 10.1080/21691401.2017.1388249
DO - 10.1080/21691401.2017.1388249
M3 - Article
C2 - 29141446
AN - SCOPUS:85034211542
VL - 46
SP - 1659
EP - 1670
JO - Artificial Cells, Nanomedicine and Biotechnology
JF - Artificial Cells, Nanomedicine and Biotechnology
SN - 2169-1401
IS - 8
ER -