Hepatocyte growth factor did not enhance the effects of bone marrow-derived mesenchymal stem cells transplantation on cardiac repair in a porcine acute myocardial infarction model

Objective To evaluate the impact of combined therapy with transplanting bone marrow-derived mesenchymal stem cells (BM-MSCs) via noninfarct-relative artery and hepatocyte growth factor (HGF) in a porcine myocardial infarction (MI) model. Methods BM-MSCs were obtained from pig bone marrow, expanded in vitro with a purity of 50%. MI was induced by ligating the distal left anterior descending artery in pigs. Eighteen animals received BM-MSCs cells (5×106/ml, n=6), BM-MSCs cells (5×106/ml ) plus HGF (4×109 pfu, n=6) or equal volume culture medium (IMDM) via non-infarct-related artery at four weeks after MI. Gated myocardial perfusion imaging and coronary angiography were performed before and four weeks after transplantations. Histological examination was also performed 4 weeks after transplantation. Results LVEF measured by gated myocardial perfusion imaging was similar among groups before transplantation and significantly increased in BM-MSCs (45±3 vs. 34±2%, P0.05) or BM-MSCs+HGF (46±6 vs. 34±3%, P0.05) treated animals while remained unchanged in IMDM (30±3 vs. 32±2%) treated animals 4 weeks post transplantation. Similarly, capillary density was also significantly higher and myocardial perfusion defect scores significantly decreased in BM-MSCs or BM-MSCs+HGF treated hearts than that in IMDM treated hearts. However, all these changes were similar between BM-MSCs and BM-MSCs+HGF groups. Rentrop score was similar before and 4 weeks after transplantation among various groups. Conclusion HGF in combination with BM-MSCs transplantation did not enhance the cardiac repair effects of BM-MSCs transplantation alone and BM-MSCs transplantation did not improve collateral circulation in this model.