Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion

Tang, Junming; Xie, Qiyang; Pan, Guodong; Wang, Jianing; Wang, Mingjiang
August 2006
European Journal of Cardio-Thoracic Surgery;Aug2006, Vol. 30 Issue 2, p353
Academic Journal
Abstract: Objective: The effect of transplanted mesenchymal stem cells (MSCs) on the left ventricular (LV) function and morphology in a rat myocardial infarct heart with reperfusion model were analyzed. Methods: One week after 60min of myocardial ischemia and reperfusion by left anterior descending artery (LAD) occlusion, 1.0×107 6-diamidino-2-phenylindole (DAPI)-labeled MSCs were injected into the infarcted myocardium and compared with controls, and sham-operated rats, in which a cell-free serum medium was injected into the infarcted region or the myocardial wall, respectively. Measurement of vascular endothelial growth factor (VEGF) expression 1 week after MSC injection using Western blot analysis (n =5), and immunohistochemical staining using HE staining and fluorescent microscopy of the DAPI-positive regions from MSC implantation, cTnT immunostaining of potential myocardial-like cells, and SM-actin and CD31 immunostaining demonstrating neovascular transformation of implanted MSCs 1 week, 2 weeks and 4 weeks after transplantation (n =5). Hemodynamic measurements were performed after 4 weeks in vivo. Subsequently, hearts were quickly removed and cut for histological analysis using HE staining with measurement of the infracted LV-area, the LV-wall thickness within the scar segment compared to non-infarcted scar segments, and the capillary density counting capillary vessels with 400× light microscopy (n =10). Results: Measurement of hemodynamics 4 weeks after transplantation in vivo showed LV function to be significantly greater in MSCs than in the control group. Semi-quantitative histomorphometric examinations showed a significantly lower infract size, a greater LV-wall thickness, and a lower Hochman-Choo expansion index in the MSC-treated group compared to the control group. Immunofluorescence demonstrated that transplanted MSCs were positive for cTnT, suggesting that a small number of transplanted MSCs can differentiate into cardiomyocytes. Other MSCs were positive for CD31 and SM-actin. The transplanted MSCs in MI area had significantly higher expression rates of cTnT, CD31 and SM-actin 2 weeks after transplantation. HE staining showed marked augmentation of neovascularization in the MSC group. Semi-quantitative analysis demonstrated that capillary density was significantly higher in the MSC group than in the control group. Conclusion: Implanted MSCs could improve cardiac structure and function through the combined effect of myogenesis and angiogenesis.


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