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Rapamycin-Preactivated Autophagy Enhances Survival and Differentiation of Mesenchymal Stem Cells After Transplantation into Infarcted Myocardium.
- Source :
-
Stem Cell Reviews & Reports . Apr2020, Vol. 16 Issue 2, p344-356. 13p. - Publication Year :
- 2020
-
Abstract
- Stem cell transplantation has been limited by poor survival of the engrafted cells in hostile microenvironment of the infarcted myocardium. This study investigated cytoprotective effect of rapamycin-preactivated autophagy on survival of the transplanted mesemchymal stem cells (MSCs). MSCs isolated from rat bone marrow were treated with 50 nmol/L rapamycin for 2 h, and then the cytoprotective effect of rapamycin was examined. After intramyocardial transplantation in rat ischemia/reperfusion models, the survival and differentiation of the rapamycin-pretreated calls were accessed. After treatment with rapamycin, autophagic activities and lysososme production of the cells were increased significantly. In the condition of short-term or long-term hypoxia and serum deprivation, the apoptotic cells in rapamycin-pretreated cells were less, and secretion of HGF, IGF-1, SCF, SDF-1 and VEGF was increased. After transplantation of rapamycin-pretreated cells, repair of the infarcted myocardium and restoration of cardial function were enhanced dramatically. Expression of HGF, IGF-1, SCF, SDF-1, VEGF, HIF-1α and IL-10 in the myocardium was upregulated, while expression of IL-1β and TNF-α was downregulated. Tracing of GFP and Sry gene showed that the survival of rapamycin-pretreated cells was increased. Cardiomyogenesis and angiogenesis in the infarcted myocardium were strengthened. Some rapamycin-pretreated cells differentiated into cardiomyocytes or endothelial cells. These results demonstrate that moderate preactivation of autophagy with rapamycin enhances the survival and differentiation of the transplanted MSCs. Rapamycin-primed MSCs can promote repair of the infarcted myocardium and improvement of cardiac function effectively. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15508943
- Volume :
- 16
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Stem Cell Reviews & Reports
- Publication Type :
- Academic Journal
- Accession number :
- 142683707
- Full Text :
- https://doi.org/10.1007/s12015-020-09952-1