Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy.
BACKGROUND
Pluripotent mesenchymal stem cells (MSCs) differentiate into a variety of cells, including cardiomyocytes and vascular endothelial cells. However, little information is available about the therapeutic potency of MSC transplantation in cases of dilated cardiomyopathy (DCM), an important cause of heart failure.


RESULTS
We investigated whether transplanted MSCs induce myogenesis and angiogenesis and improve cardiac function in a rat model of DCM. MSCs were isolated from bone marrow aspirates of isogenic adult rats and expanded ex vivo. Cultured MSCs secreted large amounts of the angiogenic, antiapoptotic, and mitogenic factors vascular endothelial growth factor, hepatocyte growth factor, adrenomedullin, and insulin-like growth factor-1. Five weeks after immunization, MSCs or vehicle was injected into the myocardium. Some engrafted MSCs were positive for the cardiac markers desmin, cardiac troponin T, and connexin-43, whereas others formed vascular structures and were positive for von Willebrand factor or smooth muscle actin. Compared with vehicle injection, MSC transplantation significantly increased capillary density and decreased the collagen volume fraction in the myocardium, resulting in decreased left ventricular end-diastolic pressure (11+/-1 versus 16+/-1 mm Hg, P<0.05) and increased left ventricular maximum dP/dt (6767+/-323 versus 5138+/-280 mm Hg/s, P<0.05).


CONCLUSIONS
MSC transplantation improved cardiac function in a rat model of DCM, possibly through induction of myogenesis and angiogenesis, as well as by inhibition of myocardial fibrosis. The beneficial effects of MSCs might be mediated not only by their differentiation into cardiomyocytes and vascular cells but also by their ability to supply large amounts of angiogenic, antiapoptotic, and mitogenic factors.
Nagaya
Noritoshi
N
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan. nnagaya@ri.ncvc.go.jp
Kangawa
Kenji
K
Itoh
Takefumi
T
Iwase
Takashi
T
Murakami
Shinsuke
S
Miyahara
Yoshinori
Y
Fujii
Takafumi
T
Uematsu
Masaaki
M
Ohgushi
Hajime
H
Yamagishi
Masakazu
M
Tokudome
Takeshi
T
Mori
Hidezo
H
Miyatake
Kunio
K
Kitamura
Soichiro
S
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005355:Fibrosis; D006133:Growth Substances / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology; D018919:Neovascularization, Physiologic; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014463:Ultrasonography
D006133:Growth Substances