title: Ultrastructural features of ischemic tissue following application of a bio-membrane based progenitor cardiomyocyte patch for myocardial infarction repair.
abstract: OBJECTIVE
  Implantation of cell-sheets into damaged regions of the heart after myocardial infarction (MI) has been shown to improve heart function. However, the tissue morphology following application of induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) has not been studied in detail at the level afforded by electron microscopy. We hypothesized that increasing the number of CM derived from iPSC would increase the effectiveness of cell-sheets used to treat ischemic cardiomyopathy. We report here on the ultrastructural features after application of a bio-membrane 'cell patch'.
  
  
  METHODS
  iPSC-derived progenitor cells were transduced using lentivirus vectors with or without NCX1 promoter. iPSC-CM sheets were transplanted over the transmural MI region in a mouse model of regional ischemic cardiomyopathy. Mice were divided into four groups, 1) Sham; 2) MI; 3) MI + iPSC without NCX1 treated cells (MI + iPSCNull) and 4) MI + iPSC receiving NCX1 promoter treated cells (MI + iPSCNCX1). Echocardiography was performed 4 weeks after cell patch application, followed by histological and transmission electron microscopy (TEM) analysis.
  
  
  RESULTS
  Large numbers of transplanted CM were observed with significant improvements in left ventricular performance and remodeling in group 4 as compared with group 3. No teratoma formation was detected in any of the treatment groups.
  
  
  CONCLUSIONS
  Manipulation of iPSC yields large numbers of iPSC-CM and favorable morphological and ultrastructural tissue changes. These changes have the potential to enhance current methods used for restoration of cardiac function after MI.
authors.affiliation: Department of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan; Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Dehua
authors.initials: D
authors.lastname: Chang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Mashhood
authors.initials: M
authors.lastname: Wani
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Christian
authors.initials: C
authors.lastname: Paul
authors.affiliation: Department of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Millard
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Yigang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology* / Q000601:surgery; D017202:Myocardial Ischemia / Q000473:pathology* / Q000601:surgery; D009206:Myocardium / Q000648:ultrastructure*; D032383:Myocytes, Cardiac / Q000637:transplantation*; D020257:Ventricular Remodeling