Attenuation of autoimmune myocarditis in rats by mesenchymal stem cell transplantation through enhanced expression of hepatocyte growth factor.
Mesenchymal stem cells (MSCs) have various effects, including angiogenic, myogenic, and paracrine actions. In this study, we determined whether MSC transplantation attenuates experimental autoimmune myocarditis (EAM). The mechanisms involved were also investigated. Male Lewis rats were immunized with myosin to establish EAM on day 0. MSCs, isolated from isogenic rats, were injected directly into the myocardium on day 14 (group MSC-2W), day 21 (group MSC-3W), or day 28 (group MSC-4W). In the MSC transplantation groups, cardiac systolic function detected by echocardiography was significantly improved, the EAM affected area determined by histological examination was significantly decreased, and capillary density was increased compared to that in the control groups. Expression of hepatocyte growth factor protein was enhanced by MSC transplantation. MSC transplantation inhibited myocardial expression of interleukin-2, -6, and -10 mRNAs. MSC transplantation reduces the severity of EAM by inducing neovascularization and inhibiting inflammatory cytokine production. Enhanced expression of hepatocyte growth factor was associated with these effects. Autoimmune myocarditis may be a good clinical target for MSC transplantation.
Okada
Hiroyuki
H
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Suzuki
Jun-ichi
J
Futamatsu
Hideki
H
Maejima
Yasuhiro
Y
Hirao
Kenzo
K
Isobe
Mitsuaki
M
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000378:metabolism* / Q000628:therapy*; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009205:Myocarditis / Q000209:etiology / Q000378:metabolism* / Q000628:therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D007378:Interleukins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor