| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
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
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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
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