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Attenuation of autoimmune myocarditis in rats by mesenchymal stem cell transplantation through enhanced expression of hepatocyte growth factor.

Abstract
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.
AuthorsHiroyuki Okada, Jun-ichi Suzuki, Hideki Futamatsu, Yasuhiro Maejima, Kenzo Hirao, Mitsuaki Isobe
JournalInternational heart journal (Int Heart J) Vol. 48 Issue 5 Pg. 649-61 (Sep 2007) ISSN: 1349-2365 [Print] Japan
PMID17998774 (Publication Type: Journal Article)
Chemical References
  • Interleukins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • RNA, Messenger
  • Hepatocyte Growth Factor
Topics
  • Animals
  • Autoimmune Diseases (etiology, metabolism, therapy)
  • Disease Models, Animal
  • Hepatocyte Growth Factor (metabolism)
  • Interleukins (genetics, metabolism)
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Myocarditis (etiology, metabolism, therapy)
  • Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
  • RNA, Messenger (metabolism)
  • Rats
  • Rats, Inbred Lew

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