The Experimental Study Of Bone Marrow Mononuclear Cell Transplantation On Infarcted Cardiac Function

Acute myocardial infarction (AMI) is the most common cause of morbidity and mortality in more developed countries. Once it happeded, serious results will be produced. Cardiomyocytes respond to mitotic signals by cell hypertrophy or apoptosis rather than by cell hyperplasia, and necrotized cardiomyocytes in infarcted ventricular tissues are progressively replaced by fibroblasts to form scar tissues. Loss of cardiomyocytes leads to progressive expansion of the initial infarct area, dilation of the ventricle lumen, and dysfunction of ventricle region, which ultimately lead to death.Reseachers have thought many methods for treatment of myocardial infarction (MI) and consequent heart failure, including medical management, intervention therapy, coronary artery bypass grafting, heart transplantation, and mechanical circulatory assistant devices artificial heart, as well as other procedures, but there seems to be a ceiling of benefit. Far-ranging myocardial infarction and diffuse coronary artery pathological changes usually induce severe heart failure, which is very difficult to be reversed by above treatments. Therefore, cell transplantation has emerged as a promising approach for improving the failing heart in the past decade. Many kinds of cells have been investigated as donors for transplantation in ischemic myocardium, including cardiac muscle cells, smooth muscle cells, embryonic stem cells, bone marrow stem cells (BMSCs), skeletal myoblast cells, liver stem cells and so on. BMSCs are the most promising candidate. Firstly, BMSCs show a high capacity for differentiation into cardiomyocytes, vascular endothelial cells, and smooth muscle cells; Secondly, BMSCs differentiated cardiomyocytes can form electric-mechanism coupling with host cardiac muscle cells, and therefore contract synchronously with host cardiac muscle cells, improve cardiac function; Thirdly, BMSCs can secret a variety of growth factors to promote cell proliferation and neovascularization; Fourthly, BMSCs can be obtained by a relatively simple bone marrow aspiration, expanded in vitro with or without differentiation and re-transplanted into the patients, BMSCs can also be mobilized to peripherial blood through cytokine, and thereafter repair myocardial injury. The application of BMSCs avoids the ethical justification encountered by embryonic stem cells; Finally, autologous BMSCs transplantation eliminates the need for immunosuppresing. Therefore, many researchers prefer to BMSCs both in basical research and clinical application.The differentiation characterization of BMSCs is the most interesting. In 1995,Wakitani et al demonstrated firstly that stromal cells, a sort of BMSCs, could differentiate into cardiac muscle-like cells ex vivo after induced by 5-azacytidine (5-aza) and amphotericin B. Makino et al discovered that stromal cells colony could differentiated into contracting cardiac muscle-like cells after induced with 3^mol/L 5-aza. However, the mechanism was not clearly described. Konieczny et al proposed that these cells contain a myogenic determination locus in a methylated state with a transcriptionally inactive phase, which becomes demethylated and transcriptionally active with 5-aza causing the cells to differentiate into myogenic cells.Furthermore, angiogenesis has recently been developed as a therapeutic method for severe ischemic heart disease in order to improve cardiac function and life-quality of patients. Numerous growth factors have been used to promote collateral circulation in recent human I trials, and the preliminary results were favourable. Vascular endothelial growth factor (VEGF) is a promising therapeutic reagent for treating myocardial infarction by inducing angiogenesis.Therefore, 5-aza treated BMSCs transplantation to repair ischemic necrosis cardiac tissue, or increasing the number of neoformed vessels through continuous, stably, and effectively expressing VEGF in ischemic cardiac area will be the most promising therapeutic methods. To seek a more effective therapeutic method for ischemic heart disease, we assume...