| Ischemic cardiomyopathy is a serious disease that imposes a threat to human. The primary cause of ischemic cardiomyopathy is that the damaged myocardial cells undergo necrosis and apoptosis in the development and progression of cardiovascular disease, while the mature myocardial cells do not have the ability to differentiate or proliferate, and can not fully compensate the affected function of heart muscle cells, leading to cardiac systolic and diastolic dysfunction. Mesenchymal stem cells (MSCs) have the characteristics of self-renewal, differentiation, proliferation and potential of multilineage differentiation. In addition, MSCs are easy to be cultured in vitro, have no immune rejection and ethical issues, thus are ideal for cell transplantation to treat ischemic cardiomyopathy.When transplanted into ischemic myocardium, bone marrow stem cells could differentiate into cardiomyocyte-like cells to promote angiogenesis and inhibit left ventricular remodeling, thus improving heart function in acute myocardial infarction and chronic congestive heart failure disease. However, these differentiated cardiomyocyte-like cells disappear in a short period and could not be further differentiated into neonatal cardiomyocyte. It has been shown that the activation of TLR4-MyD88-NFkB signaling pathways induces the release of a large number of inflammatory cytokines and thus causes cell damage. The pretreatment of transplant recipients with TLR4-specific ligand lipopolysaccharide(LPS) could stimulate bone marrow stem cells proliferation and activate TLR4/PI3K/Akt signaling pathway in original myocardial, promoting cell survival and inhibiting NFkB expression in TLR4-MyD88-NFkB signaling pathway. Consequently, the apoptosis of cardiomyocyte-like cells after transplantation is reduced and these cells are further induced to differentiate into cardiomyocytes.The main purpose of this study is to develop novel approach to improve bone marrow stem cell transplantation in the treatment of ischemic heart disease, and a provide useful guidance for coronary artery bypass surgery in combination with stem cells. We employed animal models to investigate whether inhibiting inflammatory response of myocardial infarction region could reduce the apoptosis of transplanted bone marrow stem cell.Objective: To characterize the change of number, distribution, and survival time in micro-environment after myocardial infarction of implanted rat bone marrow mesenchymal stem cells (BMSCs).Methods: Adult rats were randomly divided into control group, the myocardial infarction group, LPS (0.1mg/kg) pretreatment group, LPS (1mg/kg) pretreatment group, LPS (5mg/kg) pretreatment group. CM-Dil labeled bone marrow derived mesenchymal stem cells were injected into the left anterior descending artery ligation at left ventricular wall in those rats. 48h, 1, 3, 4 weeks later, the number and survival time of red fluorescent labeled MSCs were recorded in the infarcted myocardium. Simultaneously, the survival, apoptosis and the activation of intracellular signaling pathway were analyzed in the transplanted MSCs.Results: 22.8%MSCs underwent apoptosis in 0.1mg/kg LPS pretreatment group, much less than the control myocardial infarction group and other dose of LPS pretreatment group. After myocardial infarction TLR4, NFkB, and MyD88 mRNA and protein expression was significantly increased in LPS pretreatment group compared with the control group. A week later red fluorescent cells were decreased significantly in the myocardial infarction group and 0.1mg/kg LPS pretreatment group.Conclusion: The transplanted MSCs in myocardial infarction have a very low survival rate, perhaps due to the apoptosis induced by the changes in the microenvironment .Low-dose LPS pretreatment could reduce the local inflammatory reaction and the apoptosis of the transplanted bone marrow stem cells in the infarcted myocardium, thu prolonging the survival time of MSCs and improving the heart function.
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