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.