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Cell Culture and Tissue Engineering
Pretreatment of rat bone marrow mesenchymal stem cells with a combination of hypergravity and 5-azacytidine enhances therapeutic efficacy for myocardial infarction
Article first published online: 22 FEB 2011
DOI: 10.1002/btpr.558
Copyright © 2011 American Institute of Chemical Engineers (AIChE)
Additional Information
How to Cite
Ling, S.-K., Wang, R., Dai, Z.-Q., Nie, J.-L., Wang, H.-H., Tan, Y.-J., Cao, H.-Q., Huang, Z.-M., Wan, Y.-M. and Li, Y.-H. (2011), Pretreatment of rat bone marrow mesenchymal stem cells with a combination of hypergravity and 5-azacytidine enhances therapeutic efficacy for myocardial infarction. Biotechnol Progress, 27: 473–482. doi: 10.1002/btpr.558
Publication History
- Issue published online: 11 APR 2011
- Article first published online: 22 FEB 2011
- Accepted manuscript online: 22 DEC 2010 04:17PM EST
- Manuscript Revised: 23 OCT 2010
- Manuscript Received: 13 APR 2010
Funded by
- National Basic Research Program of China (973 Program). Grant Number: 2006CB705704, 2011CB707704
- National Natural Science Foundation of China. Grant Number: 30370365
- Advanced Space Medico-Engineering Research Project of China. Grant Number: SJ200810
- Abstract
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- Cited By
Keywords:
- bone marrow mesenchymal stem cells;
- hypergravity;
- cardiac repair;
- HDAC5;
- myocardial infarction
Abstract
Background and Purpose: The in vivo cardiac differentiation and functional effects of unmodified adult bone marrow mesenchymal stem cells (BMSCs) after myocardial infarction (MI) is controversial. Our previous results suggested that hypergravity promoted the cardiomyogenic differentiation of BMSCs, and thus we postulated that ex vivo pretreatment of BMSCs using hypergravity and 5-azacytidine (5-Aza) would lead to cardiomyogenic differentiation and result in superior biological and functional effects on cardiac regeneration of infarcted myocardium. Methods: We used a rat MI model generated by ligation of the coronary artery. Homogeneous rat BMSCs were isolated, culture expanded, and differentiated into a cardiac lineage by adding hypergravity (2G) for 3 days and 5-Aza (50 lmol/L, 24 h). Rats underwent BMSCs (labeled with DAPI) injection after the infarction and were randomized into five groups. Group A rats received the control medium, Group B rats received unmodified BMSCs, Group C rats received BMSCs treated with hypergravity, Group D rats received BMSCs treated with 5-Aza, and Group E rats received BMSCs treated with 5-Aza and hypergravity (n = 6). Results: After hypergravity and 5-Aza treatment, BMSCs showed positive for the early muscle and cardiac markers GATA-4, MEF-2, and Nkx2-5 with RT-PCR. We also found that hypergravity could enhance the activities of MEF-2 via promoting the nuclear export of HDAC5. The frozen section showed that the implanted BMSCs labeled with DAPI survived and angiogenesis was identified at the implantation site. In Groups B, C, D, and E rats, pre-treated BMSCs colocalized with α-actinin, and Group E rats showed a significantly larger increase in left ventricular function. Conclusions: The biological ex vivo cardiomyogenic differentiation of adult BMSCs with hypergravity and 5-Aza prior to their transplantation is feasible and appears to improve their in vivo cardiac differentiation as well as the functional recovery in a rat model of the infarcted myocardium. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011