Abstract 1278: Over-expression of GATA-4 in Bone Marrow Stem Cells Enhances Their Transdifferentiation Potential and Cardioprotection against Ischemia
We hypothesize that over-expression of GATA-4 in bone marrow stem cells (BMSCs) promotes cardiac protection and repair of ischemic myocardium.
Methods: Four types of stem cells were used: niched BMSCs; circulating or mobilized BMSCs (m-BMSCs) and GATA-4 transfected BMSCs (GATA-4-BMSCs) and control GFP-transfected BMSCs (GFP-BMSCs). The repair of ischemic heart was analysed in vivo and in vitro by transplantation of these cells into ischemic risk zone following LAD ligation or co-culturing these cells with cardiomyocytes which were isolated from neonatal rat hearts.
Results: 1. Transplantation of m-BMSC significantly improved cardiac function in LVDd (5.49±0.36mm vs 5.83±0.21mm in BMSCs, p<0.05) and in fraction shorting (16.4±3.2% vs 10.7±1.1% medium control, p<0.05), but there were no significant difference between BMSCs (14.5±2.5%) and medium control. 2. Transdifferentiation rate was significantly higher in m-BMSC than that in BMSC (26.5 ± 3.4% vs 16 ± 2.8 % in BMSCs) after 7 days in co-culture with cardiomyocytes; 3. m-BMSC was highly protective to cardiomyocytes against hypoxia (48 h) by reducing LDH release and DNA fragmentation, which was abrogated by GATA-4 neutralizing antibody (Fig. A, B⇓). 4. GATA-4 mRNA was 5-folds more in m-BMSCs than that in BMSC. 5. Over-expression of GATA-4 in BMSCs significantly improved the cardioprotection of BMSCs (Fig. C⇓). 6. Microarray assay indicated that several cytoprotective proteins were over-expressed in GATA-4-BMSCs (Fig. D⇓).
Conclusion: Over-expression of GATA-4 increases the transdifferentiation potential of BMSC into myocardial phenotypes and provides protection against ischemic injury.