A promising strategy for the treatment of ischemic heart disease: Mesenchymal stem cell-mediated vascular endothelial growth factor gene transfer in rats

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• 作者：Feng Gao ; MD^* ; Tao He ; MD^* ; HongBing Wang ; MD ; ShiQiang Yu ; MD ; DingHua Yi ; MD ; WeiYong Liu ; MD ; ZhenJie Cai ; MD ; ^{heart_xijing@hotmail.com}
• 关键词：Angiogenesis ; Cell transplantation ; Gene therapy ; Ischemic heart disease ; Mesenchymal stem cells ; Vascular endothelial growth factor
• 刊名：Canadian Journal of Cardiology
• 出版年：2007
• 出版时间：September 2007
• 年：2007
• 卷：23
• 期：11
• 页码：891-898
• 全文大小：793 K

文摘

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Background

Treatment of ischemic heart disease (IHD) remains a worldwide problem. Gene therapy, and recently, cell transplantation, have made desirable progress. A combination of appropriate stem cells and angiogenic genes appears promising in treating IHD.

Objective

To study the results of angiogenesis and myogenesis induced by transplantation of the adenovirus carrying human vascular endothelial growth factor 165 (Ad-hVEGF₁₆₅)-transfected mesenchymal stem cells (MSCs) in IHD compared with direct MSC transplantation or Ad-hVEGF₁₆₅ delivery.

Methods

Cultured MSCs were transfected by Ad-hVEGF₁₆₅, and secreted VEGF was measured by ELISA in vitro. Ad-hVEGF₁₆₅-transfected MSCs (MSC/VEGF group), MSCs (MSC group), AdhVEGF₁₆₅ (VEGF group) or a serum-free medium (control group) was injected into syngeneic Wistar rats immediately after left coronary artery occlusion. All cells were marked with CM-DiI (Molecular Probes, USA) before transplantation. One week after treatment, messenger RNA expression of hVEGF₁₆₅ in the MSC/VEGF group was found to be significantly higher than in other groups by reverse transcriptase-polymerase chain reaction analysis. One month after cell transplantation, left ventricular (LV) ejection fraction, capillary density of the infarcted region, infarct size and hemodynamic parameters (including LV end-diastolic pressure, LV+dP/dt and LV¨CdP/dt) were measured and immunohistochemical analysis was performed.

Results

A high level of VEGF was expressed by Ad-hVEGF₁₆₅-transfected MSCs. LV ejection fraction, mean capillary density of the infarcted region and hemodynamic parameters were significantly improved in the MSC/VEGF group compared with the MSC group, the VEGF group and the control group (P<0.001 for all). Partly transplanted MSCs showed the cardiomyocyte phenotype, expressed desmin and cardiac troponin T, and resulted in angiogenesis in the ischemic myocardium. However, a few transplanted MSCs incorporated into the vascular structure and most of the new vascular components were host-derived.

Conclusions

The combined strategy of MSC transplantation and VEGF gene therapy can produce effective myogenesis and hostderived angiogenesis, resulting in the prevention of progressive heart dysfunction after myocardial infarction.