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Am J Physiol Heart Circ Physiol (July 29, 2004). doi:10.1152/ajpheart.01071.2003
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Submitted on November 10, 2003
Accepted on July 13, 2004

Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis

Noritoshi Nagaya1*, Takafumi Fujii1, Takashi Iwase1, Hajime Ohgushi1, Takefumi Itoh1, Masaaki Uematsu1, Masakazu Yamagishi1, Hidezo Mori1, Kenji Kangawa1, and Soichiro Kitamura1

1 Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Suita, Osaka, Japan

* To whom correspondence should be addressed. E-mail: nagayann{at}hsp.ncvc.go.jp.

Mesenchymal stem cells (MSCs) are pluripotent cells which differentiate into a variety of cells including cardiomyocytes and endothelial cells. However, little information is available regarding the therapeutic potency of systemically delivered MSCs for myocardial infarction. Accordingly, we investigated whether intravenously transplanted MSCs induce angiogenesis and myogenesis and improve cardiac function in rats with acute myocardial infarction. MSCs were isolated from bone marrow aspirates of isogenic adult rats and expanded ex vivo. Three hours after coronary ligation, 5 x 106 MSCs (MSC group, n = 12) or vehicle (Control group, n = 12) was intravenously administered to Lewis rats. Transplanted MSCs were preferentially attracted to the infarcted myocardium but not to the noninfarcted myocardium. The engrafted MSCs were positive for cardiac markers: desmin, cardiac troponin T, and connexin-43. On the other hand, some of the transplanted MSCs were positive for von Willebrand factor and formed vascular structures. Capillary density was markedly increased after MSC transplantation. Cardiac infarct size in the MSC group was significantly smaller than that in the Control group (24 ± 2 versus 33 ± 2%, p < 0.05). MSC transplantation decreased left ventricular end-diastolic pressure and increased left ventricular maximum dP/dt (both p < 0.05 vs. Control group). These results suggest that intravenous administration of MSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium.




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