title: Functionally competent cardiac stem cells can be isolated from endomyocardial biopsies of patients with advanced cardiomyopathies.
abstract: BACKGROUND
  Two categories of cardiac stem cells (CSCs) with predominantly myogenic (mCSC) and vasculogenic (vCSC) properties have been characterized in the human heart. However, it is unknown whether functionally competent CSCs of both classes are present in the myocardium of patients affected by end-stage cardiac failure, and whether these cells can be harvested from relatively small myocardial samples.
  
  
  OBJECTIVE
  To establish whether a clinically relevant number of mCSCs and vCSCs can be isolated and expanded from endomyocardial biopsies of patients undergoing cardiac transplantation or left ventricular assist device implantation.
  
  
  RESULTS
  Endomyocardial biopsies were collected with a bioptome from the right side of the septum of explanted hearts or the apical LV core at the time of left ventricular assist device implantation. Two to 5 biopsies from each patient were enzymatically dissociated, and, after expansion, cells were sorted for c-kit (mCSCs) or c-kit and KDR (vCSCs) and characterized. mCSCs and vCSCs constituted 97% and 3% of the c-kit population, respectively. Population doubling time averaged 27 hours in mCSCs and vCSCs; 5×10(6) mCSCs and vCSCs were obtained in 28 and 41 days, respectively. Both CSC classes possessed significant growth reserve as documented by high telomerase activity and relatively long telomeres. mCSCs formed mostly cardiomyocytes, and vCSCs endothelial and smooth muscle cells.
  
  
  CONCLUSIONS
  The growth properties of mCSCs and vCSCs isolated from endomyocardial biopsies from patients with advanced heart failure were comparable to those obtained previously from larger myocardial samples of patients undergoing elective cardiac surgery.
authors.affiliation: Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. panversa@partners.org
authors.forename: Domenico
authors.initials: D
authors.lastname: D'Amario
authors.forename: Claudia
authors.initials: C
authors.lastname: Fiorini
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Campbell
authors.forename: Polina
authors.initials: P
authors.lastname: Goichberg
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sanada
authors.forename: Hanqiao
authors.initials: H
authors.lastname: Zheng
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoda
authors.forename: Marcello
authors.initials: M
authors.lastname: Rota
authors.forename: John M
authors.initials: JM
authors.lastname: Connell
authors.forename: Robert P
authors.initials: RP
authors.lastname: Gallegos
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Welt
authors.forename: Michael M
authors.initials: MM
authors.lastname: Givertz
authors.forename: Richard N
authors.initials: RN
authors.lastname: Mitchell
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.forename: Jan
authors.initials: J
authors.lastname: Kajstura
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.forename: Piero
authors.initials: P
authors.lastname: Anversa
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000473:pathology* / Q000502:physiology*; D000368:Aged; D001706:Biopsy; D009202:Cardiomyopathies / Q000473:pathology* / Q000503:physiopathology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D016615:Telomere / Q000473:pathology