| BackgroundTransplantation of stem cell is a promising method for the treatment of myocardial infarction. Mesenchymal stem cells (MSCs) can secrete vascular growth factors, enhance angiogenesis, improve heart function and differentiate into endothelial cells or cardiomyocytes in a specific environment. But most of the engrafted stem cells will be killed in the infarcted zone because of the harsh environment such as ischemia/reperfusion injury and inflammatory factors, which may decrease the efficacy of stem cells transplantation. It is able to increase anti-apoptotic ability of the stem cells and promote their effective differentiation towards myocardial cells directly and indirectly by pretreating the stem cells with cytokines, drugs or chemical compounds, or modifying gene expression to promote cell adhesion, survival or angiogenesis for repairing ischemic myocardium and improving heart function after transplantation of the stem cells.ObjectiveTo study if ADMSCs pretreated with bFGF could improve the survival rate of the transplanted cells and attenuates cardiac function of MI rats and provide experimental proof for clinical therapy of ischemic cardiac diseases with ADMSCs transplantation.Methods1ADMSCs were isolated from inguinal subcutaneous fatty tissues of female mice (30-50g body weight) and the3th generation ADMSCs were used in our experiment. The cells were treated with bFGF to initiate their differentiation towards cardiomyocytes before transplantation.2Models of myocardial infarction were established by ligating the anterior descending branch of the left coronary artery in female SD rats. The rat models were randomly divided into four groups according to the different preprocessing of cell before transplantation, The myocardial tissue of the infarction area was collected at different time points after ligation of the artery. The sections of the tissue were stained with HE and Masson trichroe Pathologic changes of the myocardial tissue of the infarction area were detected. One hour after ligation of the artery, ADMSCs,5-aza-ADMSCs and bFGF-pretreated ADMSCs were transplanted into the border of the infarction area, respectively. Changes of the heart activities were assessed with M-mode echocardiography at one week, two weeks, three weeks and four weeks after cell transplantation. The survival rate of ADMSCs after transplantation was examined using situ fluorescent hybridization.Results1The experimental cells expressing CD29and CD90, without CD45were proved to be ADMSCs by flow cytometry.2After coronary artery ligation, left ventricular anterior wall was pale, heart was enlarged, left atrial appendage was congestive, ventricular contraction was decreased, and clear lines were seen with the infarcted area, which indicated that the animal model was successful.3One week after infarction, cardiac function tests found that compared with the MI group, left ventricular end diastolic diameter (LVDd) in BFGF-pretreated ADMSCs group was not significantly reduced, left ventricular ejection fraction (EF) was not significantly increased, either (n=10, p>0.05). But after4weeks, LVDd and LVDs of BFGF-pretreated ADMSCs group were significantly reduced than1week after infarction in the same group and MI group, and FS and EF was also significantly improved (n=10, P <0.05). HE stain and MASSON stain showed there was scar proliferation and new vessels formation in the infarcted myocardium. ConclusionADMSCs pretreated with bFGF treating myocardial infarction could improve the survival rate of the transplanted cells and attenuates cardiac function which is better than pure stem cells transplantation. |
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