title: Pediatric End-Stage Failing Hearts Demonstrate Increased Cardiac Stem Cells.
abstract: BACKGROUND
  We sought to determine the location, expression, and characterization of cardiac stem cells (CSCs) in children with end-stage heart failure (ESHF). We hypothesized ESHF myocardium would contain an increased number of CSCs relative to age-matched healthy myocardium, and ESHF-derived CSCs would have diminished functional capacity as evidenced by reduced telomere length.
  
  
  METHODS
  Tissue samples were obtained from the explanted hearts of children undergoing heart transplantation with ESHF, defined as New York Heart Association class III or IV and ejection fraction less than 0.20, and from age-matched congenital heart disease patients with normal myocardium. The expression profile of cardiac-specific stem cell markers was determined using quantitative real time polymerase chain reaction and immunofluorescence. Cardiac stem cell growth reserve was assessed with telomere length.
  
  
  RESULTS
  There were 15 ESHF and 15 age-matched congenital heart disease patients. End-stage heart failure myocardium demonstrated increased expression of c-kit(+) and islet-1(+) CSCs by 2.0- and 2.5-fold, respectively, compared with myocardium from congenital heart disease patients. There was no difference in expression of c-kit(+) CSCs with advancing age from infants to children in ESHF myocardium. The c-kit(+) CSCs isolated from ESHF patients demonstrated significantly reduced telomere length, suggesting a diminished functional capability in these cells (8.1 ± 0.6 kbp versus 6.3 ± 0.3 kbp; p = 0.015).
  
  
  CONCLUSIONS
  End-stage heart failure myocardium demonstrated an age-independent increase in CSCs relative to healthy myocardium; however, these CSCs from ESHF patients may have diminished proliferative ability and reduced functionality as an autologous cell therapy candidate. Further investigation is necessary to determine the role of ESHF-derived CSCs within the myocardium.
authors.affiliation: Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Brody
authors.initials: B
authors.lastname: Wehman
authors.affiliation: Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Sudhish
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Rachana
authors.initials: R
authors.lastname: Mishra
authors.affiliation: Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Yin
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Colletti
authors.affiliation: Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Zachary N
authors.initials: ZN
authors.lastname: Kon
authors.affiliation: Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Srinivasa Raju
authors.initials: SR
authors.lastname: Datla
authors.affiliation: Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Osama T
authors.initials: OT
authors.lastname: Siddiqui
authors.affiliation: Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Keerti
authors.initials: K
authors.lastname: Balachandran
authors.affiliation: Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland. Electronic address: skaushal@smail.umaryland.edu.
authors.forename: Sunjay
authors.initials: S
authors.lastname: Kaushal
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D012720:Severity of Illness Index; D013234:Stem Cells / Q000502:physiology; D016615:Telomere
chemical_list: D019009:Proto-Oncogene Proteins c-kit