Abstract 9399: GATA-4 Enhances MSC Mediated Cardioprotection in Acute Myocardial Infarction via Promoting Secretion of Paracrine Factors
A growing body of evidence suggests that the paracrine action of mesenchymal stem cells (MSC) may be of a great importance to stem cell mediated cardioprotection. We hypothesized that overexpression of GATA-4 can enhance MSC mediated cardioprotection against ischemia by releasing cytoprotective factors.
Methods and Results: MSCs harvested from rat bone marrow were transduced with GATA-4 (MSCGATA-4) using the murine stem cell virus (MSCV) retroviral expression system; control cells were either untransfected (MSCbas) or GFP-transfected (MSCnull). Over-expression of GATA-4 in MSC was confirmed with immunostaining, quantitative real time PCR and western blotting. Cytoprotection was assessed by lactate dehydrogenase (LDH) release and annexin-V staining. Significantly increased native cardiomyocyte survival was observed following co-culture with MSCGATA-4 in a dual-chamber system (Fig. A) or treatment with MSCGATA-4 conditioned medium (CdM-GATA-4) (Fig. B). The secretion of VEGF and IGF-1, as well as clusterin from MSCGATA-4 was significantly increased. Peri-infarct intramyocardial delivery of MSCGATA-4 was done after an acute myocardial infarction model was developed in SD rats by ligation of the left anterior descending coronary artery. Echocardiography showed significantly preserved heart function post engraftment at the 7th day in MSCGATA-4 treated animals (Fig. C1). Histological studies showed an increased cardiomyocyte survival accompanied by a reduced infarction size in MSCGATA-4 (Fig. C2) treated animals.
Conclusions: GATA-4 based genetic engineered MSC showed increase native cardiomyocyte survival, which may represent a novel and efficient therapeutic approach for heart failure.
- © 2010 by American Heart Association, Inc.