title: Treatment with hESC-Derived Myocardial Precursors Improves Cardiac Function after a Myocardial Infarction.
abstract: BACKGROUND
  We previously reported the generation of a reporter line of human embryonic stem cells (hESCs) with enhanced green fluorescent protein (eGFP) expression driven by the α-myosin heavy chain (αMHC) promoter. The GFP+/αMHC+ cells derived from this cell line behave as multipotent, human myocardial precursors (hMPs) in vitro. In this study, we evaluated the therapeutic effects of GFP+/αMHC+ cells isolated from the reporter line in a mouse model of myocardial infarction (MI).
  
  
  METHODS
  MI was generated in immunodeficient mice. hMPs were injected into murine infarcted hearts under ultrasound guidance at 3 days post-MI. Human fetal skin fibroblasts (hFFs) were injected as control. Cardiac function was evaluated by echocardiography. Infarct size, angiogenesis, apoptosis, cell fate, and teratoma formation were analyzed by immunohistochemical staining.
  
  
  RESULTS
  Compared with control, hMPs resulted in improvement of cardiac function post-MI with smaller infarct size, induced endogenous angiogenesis, and reduced apoptosis of host cardiomyocytes at the peri-infarct zone at 28 days post-MI.
  
  
  CONCLUSIONS
  Intramyocardial injection of hMPs improved cardiac function post-MI. The engraftment rate of these cells in the myocardium post-MI was low, suggesting that the majority of effect occurs via paracrine mechanisms.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, 94143, United States of America.
authors.forename: Jianqin
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, 94143, United States of America.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Gaur
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, 94143, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, 94143, United States of America.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Sievers
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, 94143, United States of America.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Woods
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, 94143, United States of America.
authors.forename: Julian
authors.initials: J
authors.lastname: Aurigui
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, 94143, United States of America; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, 94143, United States of America.
authors.forename: Harold S
authors.initials: HS
authors.lastname: Bernstein
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, 94143, United States of America; Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, 94143, United States of America; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, 94143, United States of America.
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D004452:Echocardiography; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006321:Heart / Q000503:physiopathology; D006334:Heart Function Tests; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology*; D018919:Neovascularization, Physiologic
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins