Mechanisms of the protective effects of BMSCs promoted by TMDR with heparinized bFGF-incorporated stent in pig model of acute myocardial ischemia

Abstract

This study investigates the mechanism by which transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor incorporated degradable stent implantation (TMDRSI) enhanced effects of bone marrow mesenchymal stem cells (BMSCs) transplantation against acute ischemic myocardial injury. After the mid-third of left anterior descending artery was ligated, miniswine were divided into none-treatment group (control,n= 6), BMSCs implantation group (C,n= 6), TMDRSI group (TS,n= 6) and TMDRSI and BMSCs implantation group (TSC,n= 6). Two channels of 3.5 mm diameter were established by a self-made drill in the ischemic region, into which a stent was implanted for the TS and TSC groups. Autologous BMSCs were transplanted into the ischemic region in C group or around the channels in TSC group. Expression of von Willebrand factor, vascular endothelial growth factor, interleukin-1β, transforming growth factor-β 3, cell proliferation and apoptosis, histological and morphological analyses, myocardial remodelling and cardiac function were evaluated at different time-points. Six weeks after the operation, the above indices were significantly improved in TSC group compared with others (P< 0.05), though C and TS groups also showed better results than the control group (P< 0.05). The new method was shown to have activated paracrine pathway of transplanted BMSCs, increased survival and differentiation of such cells, and enhanced effects of BMSCs transplantation on myocardial remodelling, which may provide a new strategy for cell therapies against acute ischemic myocardial injury. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.