title: Allogeneic transplantation of fetal membrane-derived mesenchymal stem cell sheets increases neovascularization and improves cardiac function after myocardial infarction in rats.
abstract: BACKGROUND
  Mesenchymal stem cell (MSC) transplantation has been pursued as a new method to repair damaged myocardium. We focused on the fetal membrane (FM) as an alternative source to bone marrow (BM)-derived MSCs. In this study, we investigated whether transplantation of allogeneic FM-MSC sheets could attenuate myocardial dysfunction in a rat chronic myocardial infarction (MI) model.
  
  
  METHODS
  Sheets of allogeneic FM-MSC or autologous BM-MSC were transplanted into the scarred myocardium 4 weeks after coronary ligation.
  
  
  RESULTS
  Four weeks after transplantation, both allogeneic FM-MSC and autologous BM-MSC sheets had significantly improved cardiac function and reduced myocardial fibrosis compared with the untreated MI group. In both MSC sheet-transplanted groups, the peri-infarct regional capillary density was increased. Some engrafted MSCs formed vascular structures and were positive for lectin I and α-smooth muscle actin. The numbers of engrafted cells and differentiated cells were very low after both types of MSC sheet transplantation. CD3 T cells did not increase in the transplantation site, but CD163 M2 macrophages increased in the groups transplanted with allogeneic FM-MSC and autologous BM-MSC.
  
  
  CONCLUSIONS
  Transplantation of allogeneic FM-MSC or autologous BM-MSC sheets attenuated myocardial dysfunction in a rat MI model to a similar degree. The engraftment rate of transplanted cells and immune cell infiltration into the transplanted area did not differ between the two types of MSC transplants. M2 macrophage induction has possible involvement in the therapeutic effects of MSC transplantation. Allogeneic FM-MSC sheet transplantation might be a new therapeutic strategy after MI.
authors.affiliation: 1 Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. 2 Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute. 3 Department of Neuropharmacology, Faculty of Pharmaceutical Science, Fukuoka University, Fukuoka, Japan. 4 National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. 5 Department of Perinatology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. 6 Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan. 7 Address correspondence to: Hiroshi Hosoda, M.D., Ph.D., Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ishikane
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamahara
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Akitake
authors.forename: Jung
authors.initials: J
authors.lastname: Kyoungsook
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Mikiya
authors.initials: M
authors.lastname: Miyazato
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005321:Extraembryonic Membranes / Q000166:cytology*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D011247:Pregnancy; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000628:therapy