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

Author:

Matsumoto Ryo1,Omura Takashi1,Yoshiyama Minoru1,Hayashi Tetsuya1,Inamoto Sakiko1,Koh Ki-Ryang1,Ohta Kensuke1,Izumi Yasukatsu1,Nakamura Yasuhiro1,Akioka Kaname1,Kitaura Yasushi1,Takeuchi Kazuhide1,Yoshikawa Junichi1

Affiliation:

1. 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.

Abstract

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 VEGF 165 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, α-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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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