title: Xenotransplantation of Bone Marrow-Derived Human Mesenchymal Stem Cell Sheets Attenuates Left Ventricular Remodeling in a Porcine Ischemic Cardiomyopathy Model.
abstract: BACKGROUND
  Bone marrow-derived autologous human mesenchymal stem cells (MSCs) are one of the most promising cell sources for cell therapy to treat heart failure. The cell sheet technique has allowed transplantation of a large number of cells and enhanced the efficacy of cell therapy. We hypothesized that the transplantation of MSC sheets may be a feasible, safe, and effective treatment for ischemic cardiomyopathy (ICM).
  
  
  RESULTS
  Human MSCs acquired from bone marrow were positive for CD73, CD90, and CD105 and negative for CD11b and CD45 by flow cytometry. Ten MSC sheets were created from a total cell number of 1×10(8) MSCs using temperature-responsive culture dishes. These were successfully transplanted over the infarct myocardium of porcine ICM models induced by placing an ameroid constrictor on the left anterior descending coronary artery without any procedural-related complications (MSC group=6: sheet transplantation; sham group=6, oral intake of tacrolimus in both groups). Premature ventricular contractions were rarely detected by Holter electrocardiogram (ECG) in the MSC group in the first week after transplantation. On echocardiography, the cardiac performance of the MSC group was significantly better than that of the sham group at 8 weeks after transplantation. On histological examination 8 weeks after transplantation, left ventricular (LV) remodeling was significantly attenuated compared with the sham group (cardiomyocyte size and interstitial fibrosis were measured). Immunohistochemistry of the von Willebrand factor showed that the vascular density in the infarct border area was significantly greater in the MSC group than the sham group. Expression of angiogenesis-related factors in the infarct border area of the MSC group was significantly greater than that of the sham group, as measured by real-time polymerase chain reaction.
  
  
  CONCLUSIONS
  Bone marrow-derived MSC sheets improved cardiac function and attenuated LV remodeling in ICM without major complications, indicating that this strategy would be applicable in clinical settings.
authors.affiliation: 1 Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine , Suita, Japan .
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawamura
authors.affiliation: 1 Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine , Suita, Japan .
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: 1 Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine , Suita, Japan .
authors.forename: Satsuki
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: 2 Medical Center for Translational Research, Osaka University Hospital , Osaka, Japan .
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.affiliation: 1 Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine , Suita, Japan .
authors.forename: Koichi
authors.initials: K
authors.lastname: Toda
authors.affiliation: 3 Department of Biostatistics, Hyogo College of Medicine , Nishinomiya, Japan .
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.affiliation: 4 Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University , Tokyo, Japan .
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: 4 Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University , Tokyo, Japan .
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.affiliation: 1 Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine , Suita, Japan .
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D013552:Swine; D020257:Ventricular Remodeling
chemical_list: D000943:Antigens, Differentiation