| After a myocardial infarction(MI) a great deal of cardiomyocytes were necrotic and lost, replaced by fibrous tissue, with expansion of the infarct area, dilation of the left ventricle, formation of a collagen scar in the ventricular wall. Ventricle is remodeling, which is the major cause of congestive heart failure. At present, drugs and percutaneous coronary intervention(PCI) therapy can not reverse ventricular remodeling. Heart transplantation is an acceptable alternative in addition to drugs treatment, however, only a small number of patients can receive heart transplantation because of the shortage of donors. Despite advances in the treatment of MI, reduced cardiac function resulting from ventricular remodeling is still a major problem. Therefore finding effective approaches to prevent remodeling is a major therapeutic challenge.Recently, it has been demonstrated that cell transplantation with bone marrow cells possibly differentiates into cardiomyocytes to replace the lost cells(myogenesis) and induce blood vessel growth(angiogenesis), which may improves cardiac function in an ischemic heart model. However, there is little evidence that bone marrow cell transplantation improves matrix remodeling and is benefit to left ventricular remodeling processes.In clinic, there are high incidence of myocardial infarction in the elderly, their autologous MSCs proliferates and differentiate slowly, it should spend more times in culture, and possibly can't catch optimum occasion to transplant cells. However, thetransplanted exogenous cells possibly survived for only a short time in the recipient heart because of immunological rejection.Therefore, the study was performed to investigate the efficiency of mesenchymal stem cells(MSCs) transplantation on ventricular remodeling and heart function after myocardial infarction in rats and compare the effects between rat MSCs and neonatal rat MSCs transplantation to observe the feasibility of using exogenous MSCs for cell therapy.Materials and MethodsRat MSCs and neonatal rat MSCs were acquired from the bone marrow of rats and neonatal rats respectively. They were isolated, purified and cultured in ex vivo, marked with bromodeoxyuridine(Brdu) before transplantation. Forty Sprague-Dawley male rats aged 2 months(220-280g body weight) were divided into four groups, rat MSCs group;neonatal rat MSCs group;control group;sham-operation group. Ten animals were used in each group. Rats were undergone ischemic procession by thoracotomy and ligation of the left anterior descending coronary artery(LAD) in the former three groups. Rats underwent thoracotomy only in sham-operation group. One hour after the LAD ligation, rats received rat MSCs(rat MSCs group), neonatal rat MSCs(neonatal rat MSCs group) cell suspension(5 X 106 cells in total, 150ul) or 150ul of PBS(control group, sham-operation group), respectively, by direct intramyocardial injection into the border of infarcts in exogenous rats. 6 weeks after transplantation, Rats' heart function, ventricular remodeling and pathologies results were measured by echocardiography, direct survey, histology and immunohistochemistry.Results1. Transplantation of MSCs decreased LV end-diastolic diameter and end-systolic diameter(0.52cm ± 0.07cm, 0.52cm ± 0.07cm vs 10.60cm ± 0.09cm, PO.05;0.37cm ± 0.08cm, 0.37cm ± 0.06cm vs 0.46cm ± 0.09cm, PO.05), improvedcardiac function, decreased weight index(2.12mg/g ± 0.11mg/g, 2.11mg/g ±0.08mg/g vs 2.24mg/g±0.13mg/g, PO.05), thickened the LV walls(2.29mm±0.33mm, 2.41mm ± 0.27mm vs 1.77mm ± 0.25mm, i><0.01), limited LV chambers(1.20 ± 0.07, 1.19 + 0.06 vs 1.44 ± 0.09, PO.O^significantly, as compared with the control. MSCs transplantation prevented cardiac dilatation and reduced collagen content. There were no significant difference between rats MSCs and neonatal rats MSCs transplanted groups.2. The numbers of blood vessels and cardiomyocytes were increased at the boundary of infarction site in the animals transplanted with MSCs(5.62 ± 0.84vessels/0.2mm2, 5.88 ± 0.67vessels/0.2mm2 vs 2.14 ± 0.55vessels/0.2mm2, P<0.0\). Collagen content was reduced(24.04%±5.71%, 25.58%±6.12% vs 41.80%±5.77%, PO.01). Brdu-labeled MSCs with oval nucleus were widely distributed.Conclusion1. MSCs transplantation has beneficial effects on ventricular remodeling processes and contributes to improvement of cardiac function. Cardiac functional benefits from intramyocardial transplantation of stem cells were associated with increased myocyte number(myogenesis) and regional blood perfusion(angiogenesis), reduced the amount of the fibrosis, prevented matrix remodeling.2. There's no obvious inflammation and immunological rejection in the host myocardium with rats MSCs and neonatal rats MSCs transplantation. Exogenous MSCs can survive and home in host infarct hearts without addition of any immunosuppressant. Allogenetic cells transplantation is feasibility.KEY WORDS... |
