Bone marrow mononuclear cell therapy limits myocardial infarct size through vascular endothelial growth factor.
No prior study has examined the effect of intravenous injection of bone marrow mononuclear cells (MNCs) on myocardial infarction size (IS). We tested the hypothesis that transplantation of MNCs decreases IS through the release of vascular endothelial growth factor (VEGF). Immediately after ligation of the left coronary artery of immunodeficient mice, PBS or MNCs were intravenously administered. Myocardial IS was significantly less in MNCs-treated mice than in PBS-treated mice. Trace experiments showed accumulation of exogenously administered MNCs into the vicinity of infarcted myocardium. Injection of MNCs did not affect capillary density after infarction, but did reduced myocardial cell apoptosis. Blockade of VEGF by a neutralizing antibody or by gene transfer of a soluble form of Flt-1 VEGF receptor diminished the IS-limiting effects of MNCs. In conclusion, injection of MNCs can reduce myocardial IS through the release of VEGF. The MNC therapy for acute myocardial infarction might improve prognosis of patients with myocardial infarction.
Hiasa
Ken-ichi
K
Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan.
Egashira
Kensuke
K
Kitamoto
Shiro
S
Ishibashi
Minako
M
Inoue
Shujiro
S
Ni
Weihua
W
Zhao
Qingwei
Q
Nagata
Shin
S
Katoh
Makoto
M
Sata
Masataka
M
Takeshita
Akira
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016026:Bone Marrow Transplantation; D003331:Coronary Vessels / Q000502:physiology; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D051379:Mice; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A