Heparin Enhances the Effects of Mesenchymal Stem Cell Transplantation in a Rabbit Model of Acute Myocardial Infarction.

Abstract

Stem cell transplantation in combination with administration of bioactive compounds has shown promising resultsin treating myocardial infraction (MI). In the current study, we investigated the effect of combining mesenchymal stem cells(MSCs) transplantation with heparin into the infarcted heart rabbits. For this purpose, 35 male New Zealand white rabbitswere randomly divided into five groups: sham, MI, MI+ MSCs, MI+ heparin and MI+MSCs+ heparin. MI was induced by30 min ligation of the left anterior descending coronary artery. The animals of MSCs and MSCs +heparin groups wereinjected cell culture containing MSCs intramyocardially into the infarct area. Functional parameters of the left ventricle byechocardiography, serum levels of VEGF by enzyme-linked immunosorbent assay, size of fibrotic area by Masson'strichrome staining, evaluation of morphology by Haematoxylin-Eosin and capillary density alkaline phosphatase stainingwere compared between groups. Ejection fraction, fractional shortening and levels of VEGF significantly improved in MSCsand MSCs + heparin group (P<0.05). The fibrotic area was significantly reduced (p=0.009) in MSC + heparin treated animalsin comparison with MSCs. Number of live cells and angiogenesis were increased significantly in MSCs + heparin groups incomparison with MSCs (p< 0.05). Although injection of MSCs significantly restored normal function of fibrotic area, wefound that administration of heparin combined with MSCs to infarcted heart of animals could have better effects on LVfunctional parameters in fibrosis area and resulted in superior therapeutic outcome in enhancing neovascularization andimproving cardiac fibrosis.