Abstract 16851: Estradiol-Treated Cardiac Stem Cells Improve Myocardial Recovery Following Acute Ischemia/Reperfusion Through Enhanced Paracrine Protection
INTRODUCTION: Cardiac stem cells (CSC) mediate cardioprotection following ischemia. However, prior research has mainly focused on studying differentiation capacities of CSC. Little is known about implication of paracrine action by CSC in protection of the ischemic heart. On the other hand, our group and others have shown that non-cardiac stem cells mediate their beneficial effects primarily via paracrine action and estrogen is implicated in promoting this stem cell-mediated protection. In this study, therefore, we hypothesized that 1) CSC are able to acutely improve cardiac function without cell differentiation following ischemia/reperfusion (I/R) and 2) 17β-estradiol (E2)-treated CSC provide greater protection of cardiac function.
METHOD: CSC were isolated from C57BL mouse hearts, and identified by flow cytometry and mRNA-qPCR. Cardiac I/R was performed in isolated mouse hearts via Langendorff. 0.1x10^6/ml CSC or E2-treated CSC (CSC treated with 100nM of E2 for 24-hr) were infused immediately prior to ischemia. Secretion of VEGF, HGF and SDF-1 by CSC and E2-treated CSC was assessed using ELISA. Hypoxia-induced myocyte injury was detected by LDH assay. Data were analyzed with two-way ANOVA or t-test, p<0.05=statistically significant.
RESULTS: Flow cytometry data revealed that CSC expressed Sca-1, CD29 and CD44 (all >90%), but did not express CD31, CD34, CD45 or CD106 (all <5%). Cardiac specific transcription factors NKX2.5, Gata4, MEF2c and Tbx5 were detected in CSC. E2-treated CSC produced higher levels of VEGF, HGF and SDF-1 compared to untreated CSC. Infusion of CSC and E2-treated CSC improved myocardial function following acute I/R with greater protection in E2-treated CSC group (graph).
CONCLUSION: Pretreatment of CSC acutely improved I/R-injured cardiac function and myocyte viability through paracrine action. E2-treated CSC may enhance this paracrine protection, suggesting that in vitro modification of CSC may improve therapeutic outcome.
- © 2011 by American Heart Association, Inc.