Abstract
Survival of stem cells following transplantation in the infarcted myocardium is a critical issue for the cell‐based therapy and preconditioning (PC) of stem cells is a method for cytoprotection. In this study, we investigated the cytoprotective effect of PC with electrical stimulation (EleS) on cardiac stem cells (CSCs) survival. Sca‐1+ CSCs were isolated from male C57BL6 mice hearts. PC of CSCs with EleS (EleSCSCs) was carried out for 3 h at 1.5 V followed by exposure to H2O2. Cytoprotective effects and cell adhesion ability were significantly increased by EleS as evaluated by TUNEL, lactate dehyrogenase release assay and adhesion assay as well as Sry gene analysis in vivo. EleS increased phosphorylation of AKT, FAK and GSK3β, and decreased pro‐apoptotic protein caspase‐3 cleavage. Pretreatment with Wortmannin, a PI3K inhibitor, and FAK inhibitor‐14 abolished the pro‐survival effects of EleS. Importantly, we found that connective tissue growth factor (Ctgf) is a key determinant for EleS‐induced CSC survival and adhesion. Furthermore, we identified miR‐378 is a potential negative regulator for Ctgf expression in EleSCSCs.In conclusion, EleS enhanced CSC survival in vitro and in vivo through AKT/FAK/CTGF/miR‐378 signaling cascade, being suggested as a novel preconditioining strategy.This work was supported by National Institutes of Health grant, [HL087246 to M.A.].
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