Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction.

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 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, alpha-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.

• Authors: 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 25 Issue 6 Pg. 1168-73 (Jun 2005) ISSN: 1524-4636 [Electronic] United States
• PMID: 15831811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• VEGFA protein, human
• Vascular Endothelial Growth Factor A

Topics

• Actin Cytoskeleton (ultrastructure)
• Animals
• Capillaries
• Cell Differentiation
• Coronary Circulation
• Genetic Therapy (methods)
• Graft Survival
• Humans
• Lac Operon
• Male
• Mesoderm (cytology)
• Microscopy, Electron
• Myocardial Infarction (pathology, therapy)
• Neovascularization, Physiologic
• Rats
• Rats, Inbred Lew
• Stem Cell Transplantation
• Stroke Volume
• Transfection
• Vascular Endothelial Growth Factor A (genetics)
• Ventricular Function, Left