Effects Of Hepatocyte Growth Factor Modified Bone Marrow Derived Meshenchymal Stem Cells On Myocardial Fibrosis And Apoptosis Of Dilated Cardiomyopathy Rats

Part oneEffects of transplantion of MSCs modified by hepatocyte growth factor on heart function of DCM model ratsObjective:BMSCs transfected with Ad-hHGF was transplanted into DCM model rats so as to investigate the changes of heart function after transplantation among every groups.Methods:Rats'bone marrow-derived MSCs were isolated using Percoll desity gradient method and according to the adherent property of MSC.Then we infected rats'MSCs with adenovirus vector encoding hHGF.Thirty-six SD rats underwent injecting intraperitoneal injection with adriamycin so as to establish heart failure model.Fourteen rats did not undergo any operation.twenty-four surviving rats that underwent injecting adriamycin were randomly divided into 3 equal groups:The MSCs-hHGF group to be injected via caudal vein with suspension of Ad-hHGF transfected MSCs after 2 weeks of the establishment of the model,the MSCs group to be injected with suspension of MSCs transfected without Ad-hHGF,and the Normal group and Model group to be injected with PBS only.To collect blood plasma from four groups rats in the different times to detect the expression of hHGF.Four weeks after the injectiong,the surviving rats underwent examination of heart functions by a physiological recorder.Results:.It showed that transfection efficency was increasing along with the increase of MOI.A nearly 100%cells were transfected when the 100 of MOI was administrated.MSC could be transfected efficiently as seed cells to accept target genes by Ad-hHGF,outcome of flow cytometer:CD90,97.70%;CD44,99.90%; CD34,2.08%;CD11,15.90%。,.Four weeks after the cells were transplanted,.the heart function of the MSCs-hHGF group and the MSC group were higher obviously than the model group(LVEDP,p＜0.05;LVSP,p＜0.05) and the MSCs-hHGF group was higher than the MSC group(LVEDP,p＜0.05;LVSP,p＜0.05).The hHGF in plasma could only be detected in the MSCs-hHGF group but another groups.Conclusions;1,That the MSCs infected by Ad-hHGF could express HGF efficiently for two weeks at least,imply that MSCs are excellent cells for cell-mediated HGF gene therapy or cell therapy.2,The heart function of the group of MSCs infected by Ad-hHGF is better than that of the group of MSCs transplantation simply,which means that HGF and MSCs could improve reciprocally heart function of DCM rats. Part twoEffects of transplantation of MSCs modified by hepatocyte growth factor on myocardial fibrosis and apoptosis of DCM ratsObjective:To research effects of transplantion of MSCs modified by HGF on myocardial fibrosis and apoptosis of DCM rats induced by adriamycin.Method:After heart function of all rats was measured,myocardial tissue collagens was observed by staining of Sirus red in supersaturated picric acid solution then the changeS ofⅠ/Ⅲcollagens was observed by polarization microscope.And the expressions of HGF,MMP-1,and TIMP-1 in myocardial cells were detected by immunohistochemical method.Myocardial cells apoptosis were detected by TUNEL methodsResult The collagen of the MSC-hHGF group shown by staining of Sirus red in supersaturated picric acid solution was much less than that of the DCM model group, (1.95±0.27%vs 7.00±0.41%),and was also less than MSC group(1.95±0.27% vs3.44±0.60%,P＜0.05).The proportion ofⅠ/Ⅲcollagen observed by polarization microscope in the MSC-hHGF group,is not only lower than that of the model group (53.56±8.57%vs 78.45±11.32%,P＜0.01),but also that of the MSCs group. (53.56±8.57%vs 66.35±10.01%,P＜0.05).The content of mmp1 of MSC-hHGF group is more than DCM model group and MSCs group And the content of the TIMP1 of MSC-hHGF group is lower than DCM but MSCs group.The content of HGFof the MSC-hHGF group is much higher than that of the DCM model group,and normal group.The amount of apoptotic cardiocyte in the MSC-hHGF group is less than DCM modelgroup(14.52±2.78%vs23.90±3.19%,p＜0.01) but MSCs groupConclusions;(1)HGF can improve suppression effect of MSCs on fibrosis of myocardial tissue(2)HGF can not help MSCs to reduce the amount of apoptosis of cardiocyte(3) HGF can improve heart function of DCM rats.by suppressing fibrosis of myocardial tissue,...