OBJECTIVETo 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.

METHODSBM-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 x 10(6)/ml, n = 6), BM-MSCs cells (5 x 10(6)/ml) plus HGF (4 x 10(9) 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.

RESULTSLVEF measured by gated myocardial perfusion imaging was similar among groups before transplantation and significantly increased in BM-MSCs (45 +/- 3 vs. 34 +/- 2%, P < 0.05) or BM-MSCs + HGF (46 +/- 6 vs. 34 +/- 3%, P < 0.05) 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.

CONCLUSIONHGF 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.