Neovascularization and cardiomyocytes regeneration in acute myocardial infarction after bone marrow stromal cell transplantation: comparison of infarct-relative and noninfarct-relative arterial approaches in swine.

摘要

BACKGROUND: Adult bone marrow stromal cells could differentiate into myogenic endothelial progenitor cells and has been investigated for the potential value in regeneration. Recently, it has been reported that bone marrow cells (BMCs) are able to repair the infracted myocardium by intracoronary transplantation via infarct-related artery in humans. Unfortunately, we cannot open the infarcted artery by traditional reperfusion therapies in some patients. We investigate the hypothesis that BMCs transplantation might get the same effect via noninfarct-relative artery. This alternative approach may have potential application in clinical practice. METHODS: A swine myocardial infarction model was established by distal left anterior descending artery ligation. Bone marrow stromal cells isolated, culture-expanded and labeled with bromodeoxyuridine (BrdU) were used as donor cells. Four weeks after coronary artery ligation, either a graft of 5x10(6) donor cells (n=12) or culture medium (n=6) was infused into infarcted area via infarct-relative artery (left coronary artery, n=6) and noninfarct-relative artery (right coronary artery, n=6). Heart function was evaluated by gate cardiac perfusion imaging before the transplantation and 4 weeks after transplantation. The donor cell localization and differentiation were identified by immunohistochemical staining for BrdU and beta-myosin heavy chain (beta-MHC) and angiogenesis was assessed by immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA) and Factor VIII. RESULTS: Gate cardiac perfusion imaging demonstrated that the cardiac function was significantly improved after the stromal cell transplantation via both infarct-relative and noninfarct-relative coronary arteries compared with control group (45.03+/-2.71 and 47.78+/-2.64 vs 30.36+/-2.76, P<0.05). Four weeks after transplantation, BrdU and beta-MHC positive cells were detected within the infarct area. Vessel densities in infarct area and infarct border area were increased significantly in both transplantation groups compared to the control group (98.68+/-5.32 and 87.49+/-6.04 vs 48.46+/-4.88, P<0.05). CONCLUSIONS: Transplantation of bone marrow stromal cell via both infarct-relative and noninfarct-relative coronary arteries improved heart function in the myocardial infarction animals by stimulating cardiomyocyte regeneration and angiogenesis.