title: Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy.
abstract: 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.
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan. nnagaya@ri.ncvc.go.jp
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Nagaya
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Takefumi
authors.initials: T
authors.lastname: Itoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwase
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Murakami
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Miyahara
authors.forename: Takafumi
authors.initials: T
authors.lastname: Fujii
authors.forename: Masaaki
authors.initials: M
authors.lastname: Uematsu
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohgushi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokudome
authors.forename: Hidezo
authors.initials: H
authors.lastname: Mori
authors.forename: Kunio
authors.initials: K
authors.lastname: Miyatake
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kitamura
mesh_terms: 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
chemical_list: D006133:Growth Substances