Collagen Remodeling Effect of Transplantation Mesenchymal Stem Cells with a Cardiac-Specific Expressing Human Vascular Endothelial Growth Factor-165 Gene in Dilated Cardiomyopathy Animal Model

Objective:To investigate the collagen remodeling effect of transplantation mesenchymal stem cells(MSCs) combined with a cardiac-specific expressing human vascular endothelial growth factor-165(hVEGF165) gene in dilated cardiomyopathy(DCM) animal model.Methods: The bone marrow-derived mesenchymal stem cells of rat were isolated,cultured and expanded ex vivo.The characteristics of those cells were identified by flow cytomery.The subjects were divided into PBS group,MSCS transplantation group(MSCS),gene therapeutic group(GENE),and MSCS transplantation combined with gene transfection group(MSCS-GENE),in which the MSCs and/or pmlc-2v-EGFP-hVEGF165 were injected into the rats' heart.After 1 month,reverse transcriptase PCR(RT-PCR) was used to detect the mRNA expressions of type I,type III collagen and human transforming growth factor β1(TGF-β1).The expressions of hVEGF165 were documented by Western blot.Results: Although the optical densities of TGF-β1 were significantly lower in MSCs-GENE group and GENE group than those in PBS group and MSCs,there were no difference between MSCs-GENE group and GENE group(P=0.910),which suggested the expressions of TGF-β1 were down-regulation in both MSCs-GENE group and GENE group.Comparison of optical density ratio of type I/III collagen,the optical densities ratios were lower in MSCs-GENE group than that in MSCs group and GENE group,but there was no statistics different(P=0.172).Though there were expressions of GAPDH in each group,but the expression of hVEGF165 were detected in MSCs-GENE group and GENE group,which suggested the target gene specifically expressing its products in myocardial.Conclusions: The mechanism of cardiac function improved by MSCs with VEGF genes may be related to the down-regulation of TGF-β1 expression,decreasing ratio of type I/III collagen,and increased myocardial compliance and attenuation of remodeling of myocardial collagen lattice.