| Background:Despite advances in medical and surgical procedures, heart failure remains a leading cause of cardiovascular morbidity and mortality. Although myocyte mitosis and the presence of cardiac precursor cells in adult hearts have recently been reported, the death of large numbers of cardiomyocytes results in the development of heart failure. Many researchers have investigated cell transplantation and considered it as an alternative treatment for heart disease. A variety of cell types have been proposed as useful candidates.It is now accepted that an adherent population of cells isolated from bone marrow is multipotential progenitor cells, which can differentiate into muscle, cartilage, bone and fat. Dramatic advances have been made in the clinical application of BM-MNCs in heart failure of ischemic origin, however, little information is available about the therapeutic potential of BM-MNCs for chronic heart failure of nonischemic origin and the beneficial effects are mediated by their differentiation into cardiomyocytes and vascular cells and by their supplying angiogenic are still a debated object.Objectives:The heart failure model was induced by rapid ventricular pacing, then we observed the feaserbility of which BM-MNCs suspension was injected into myocardium. After a month, the cardiac function was evaluated to observe if BM-MNCs can improve LVEF.The cardiac muscle specimen was detected by immunohistochemistry to observe if BM-MNCs can differentiate into cardiomyocytes, then to observe the fibrosis extent in the heart.Methods:13 healthy adult mongrel dogs of either sex, weighing between 15 and 20 kg each, were separated 2 groups randomly, and model of heart failure was produced by rapid right ventricular pacing. A pacemaker wire was introduced into the right jugular vein and positioned in the right ventricle, and transthoracic rest echocardiography was performed after 2-4 weeks of rapid right ventricular pacing, if the left ventricular ejection fraction is obviously lower, we confirmed that the model of heart failure was established. Bone marrow aspirates were passed through a density gradient to eliminate unwanted cell types, then the remaining purified BM-MNCs population was labeled with the cross-linkable membrane dye CM-Dil and were delivered via direct surgical intramyocardial injection (4-5 sites) within the cardiac apex. The control group (n=6) received saline injections in the same manner. Before injection, the cells were thoroughly washed and resuspended in a 1-ml volume of saline (3×107-1×108/ml).After 4 weeks of transplantation, echocardiography were performed to observe the cardiac function. Dogs hearts were exposed by median sternotomy and quickly removed,and sliced in a bread-loaf manner into 4 transverse sections from apex to base. Each section was separated into anterior, anterolateral, lateral, posterolateral,and posterior LV. Each section thickness was sliced in half; one half was frozen in liquid nitrogen,and the remainder was fixed in 10% formaldehyde. All specimens were labeled by FITC. Myocardial fibrosis conditions of implanted cells and its association were observed by means of collagen volume fraction and immunohistochemistry.Results:1. Four weeks later, the BM-MNCs labeled by CM-DiI and FITC were found in the transplantation group showing yellow fluorescence while in the control group labeled by FITC only green fluorescence was seen.2. Four weeks later, ejection fraction increased significantly as compared with the baseline (37.29±6.75% vs 42.14±2.79%, P<0.05) while there was no significant improvement in the control group.3.The collagen volume fraction in the transplantation group decreased significantly as compared with the control group (2±0.1%vs 6±0.5%; 2.7±0.3 %vs 5.7±0.3%;1.8±0.5% vs 4.5±0.6%, P<0.05).Conclusion:In the present study, we have demonstrated the following effects of BM-MNCs transplantation in a canine model of heart failure:(1)induction of myogenesis; (2) differentiation of transplanted MSCs into cardiomyocytes; (3) improvement of cardiac function and inhibition of ventricular remodeling,which mechanism possibly associate with the ability of inhibiting the myocardial fibrosis. |
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