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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1168.)
© 2005 American Heart Association, Inc.

Vascular Biology

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

Ryo Matsumoto; Takashi Omura; Minoru Yoshiyama; Tetsuya Hayashi; Sakiko Inamoto; Ki-Ryang Koh; Kensuke Ohta; Yasukatsu Izumi; Yasuhiro Nakamura; Kaname Akioka; Yasushi Kitaura; Kazuhide Takeuchi; Junichi Yoshikawa

From the Departments of Internal Medicine and Cardiology (R.M., T.O., M.Y., Y.N., K.A., K.T., J.Y.), Clinical Hematology and Clinical Diagnostics (K.-R.K., K.O.), and Pharmacology (Y.I.), Osaka City University Medical School, Osaka, Japan; and the Third Department of Internal Medicine (T.H., S.I., Y.K.), Osaka Medical College, Osaka, Japan.

Correspondence to Takashi Omura, Department of Internal Medicine and Cardiology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. E-mail omura{at}med.osaka-cu.ac.jp

Objective— Vascular endothelial growth factor (VEGF) plays an important role in inducing angiogenesis. Mesenchymal stem cells (MSCs) may have potential for differentiation to several types of cells, including myocytes. We hypothesized that transplantation of VEGF-expressing MSCs could effectively treat acute myocardial infarction (MI) by providing enhanced cardioprotection, followed by angiogenic effects in salvaging ischemic myocardium.

Methods and Results— The human VEGF₁₆₅ gene was transfected to cultured MSCs of Lewis rats using an adenoviral vector. Six million VEGF-transfected and LacZ-transfected MSCs (VEGF group), LacZ-transfected MSCs (control group), or serum-free medium only (medium group) were injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. At 1 week after MI, MSCs were detected by X-gal staining in infarcted region. High expression of VEGF was immunostained in the VEGF group. At 28 days after MI, infarct size, left ventricular dimensions, ejection fraction, E wave/A wave ratio and capillary density of the infarcted region were most improved in the VEGF group, compared with the medium group. Immunohistochemically, -smooth muscle actin–positive cells were most increased in the VEGF group.

Conclusions— This combined strategy of cell transplantation with gene therapy could be a useful therapy for the treatment of acute MI.

We studied cell transplantation of VEGF-expressing mesenchymal stem cells (MSCs) on rat myocardial infarction (MI). Infarct size, left ventricular dimensions, ejection fraction, E wave/A wave ratio, and capillary density were most improved in the VEGF-expressing MSCs group. In conclusion, this cell transplantation with gene therapy could be a useful treatment for MI.

Key Words: angiogenesis • gene therapy • myocardial infarction • stem cell • transplantation

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