Cell Transplantation for the Treatment of Acute Myocardial Infarction Using Vascular Endothelial Growth Factor-Expressing Mesenchymal Stem Cells

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Vascular endothelial growth factor (VEGF) may be a therapeutic reagent for ischemic region by inducing angiogenesis. Mesenchymal stem cells (MSCs) have multiple differentiated potential including cardiomyocytes. Therefore, we hypothesized that transplantation of VEGF-expressing MSCs could effectively treat myocardial infarction by providing VEGF-induced cardioprotection, followed by angiogenesis in ischemic myocardium combined with the functional benefits of MSCs-derived cells. Bone marrow mononuclear cells of Lewis rats were cultured with low glucose DMEM for MSCs outgrowth. MSCs were transfected with adenovirus expressing human VEGF_<165> and/or beta-galactosidase (lac Z). Six million of VEGF and lac Z transfected MSCs (VEGF group, n=8), lac Z transfected MSCs (Cont group, n=7), or medium only (M group, n=10) were injected into infarcted myocardium of syngeneic rat after left coronary artery occlusion for one hour. At one week after the injection, lac Z-expression cells were immunohi … More stochemically detected in VEGF group and Cont group. Moreover, positive finding against VEGF polyclonal antibody was increased in VEGF group than in Cont group. At four weeks, infarct size (VEGF; 26.3, Cont; 31.4, M; 38.0 %, P<0.05) was significantly reduced in VEGE group, compared with M group. By echocardiography assessment, left ventricular end-diastolic dimension was significantly lower in the VEGF group, compared with M group (VEGF; 9.9, Cont; 10.2, M; 10.8 mm, p<0.01). Left ventricular fractional shortening (VEGF; 20.0, Cont; 17.7, M; 10.7 %, P<0.05) and ejection fraction (VEGF; 48.3, Cont; 43.6, M; 28.6 %, P<0.05) were significantly higher in VEGF group and Cont group. By light microscopy, increased number of capillaries was observed in infarcted area of VEGF group. Under electoron microscopy, many spindle-shaped interstitial cells and small cells containing myofilaments were observed adjacent to the infarcted area both in VEGF group and Cont group. Furthermore, the spindle-shaped cells were often making point-to-point contact each other and arranged helically around a lumen in VEGF group. In conclusion, this combined strategy of cell transplantation with gene therapy could be important for the treatment of acute myocardial infarction. Less