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


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.
Matsumoto
Ryo
R
Department of Internal Medicine and Cardiology, Osaka City University Medical School, Osaka, Japan.
Omura
Takashi
T
Yoshiyama
Minoru
M
Hayashi
Tetsuya
T
Inamoto
Sakiko
S
Koh
Ki-Ryang
KR
Ohta
Kensuke
K
Izumi
Yasukatsu
Y
Nakamura
Yasuhiro
Y
Akioka
Kaname
K
Kitaura
Yasushi
Y
Takeuchi
Kazuhide
K
Yoshikawa
Junichi
J
D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000818:Animals; D002196:Capillaries; D002454:Cell Differentiation; D003326:Coronary Circulation; D015316:Genetic Therapy / Q000379:methods*; D006085:Graft Survival; D006801:Humans; D007763:Lac Operon; D008297:Male; D008648:Mesoderm / Q000166:cytology; D008854:Microscopy, Electron; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation; D013318:Stroke Volume; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D016277:Ventricular Function, Left
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A