title: Human cardiosphere-derived cells from advanced heart failure patients exhibit augmented functional potency in myocardial repair.
abstract: OBJECTIVE
  This study sought to compare the regenerative potency of cells derived from healthy and diseased human hearts.
  
  
  BACKGROUND
  Results from pre-clinical studies and the CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial support the notion that cardiosphere-derived cells (CDCs) from normal and recently infarcted hearts are capable of regenerating healthy heart tissue after myocardial infarction (MI). It is unknown whether CDCs derived from advanced heart failure (HF) patients retain the same regenerative potency.
  
  
  METHODS
  In a mouse model of acute MI, we compared the regenerative potential and functional benefits of CDCs derived from 3 groups: 1) non-failing (NF) donor: healthy donor hearts post-transplantation; 2) MI: patients who had an MI 9 to 35 days before biopsy; and 3) HF: advanced cardiomyopathy tissue explanted at cardiac transplantation.
  
  
  RESULTS
  Cell growth and phenotype were identical in all 3 groups. Injection of HF CDCs led to the greatest therapeutic benefit in mice, with the highest left ventricular ejection fraction, thickest infarct wall, most viable tissue, and least scar 3 weeks after treatment. In vitro assays revealed that HF CDCs secreted higher levels of stromal cell-derived factor (SDF)-1, which may contribute to the cells' augmented resistance to oxidative stress, enhanced angiogenesis, and improved myocyte survival. Histological analysis indicated that HF CDCs engrafted better, recruited more endogenous stem cells, and induced greater angiogenesis and cardiomyocyte cell-cycle re-entry. CDC-secreted SDF-1 levels correlated with decreases in scar mass over time in CADUCEUS patients treated with autologous CDCs.
  
  
  CONCLUSIONS
  CDCs from advanced HF patients exhibit augmented potency in ameliorating ventricular dysfunction post-MI, possibly through SDF-1–mediated mechanisms.
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Ke
authors: K
authors: Cheng
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Konstantinos
authors: K
authors: Malliaras
authors: Cedars-Sinai Heart Institute, Los Angeles, California.|Capricor Inc., Los Angeles, California.
authors: Rachel Ruckdeschel
authors: RR
authors: Smith
authors: Cedars-Sinai Heart Institute, Los Angeles, California.|Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors: Deliang
authors: D
authors: Shen
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Baiming
authors: B
authors: Sun
authors: Capricor Inc., Los Angeles, California.
authors: Agnieszka
authors: A
authors: Blusztajn
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Yucai
authors: Y
authors: Xie
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Ahmed
authors: A
authors: Ibrahim
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Mohammad Amin
authors: MA
authors: Aminzadeh
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Weixin
authors: W
authors: Liu
authors: Cedars-Sinai Heart Institute, Los Angeles, California.|Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan.
authors: Tao-Sheng
authors: TS
authors: Li
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Michele A
authors: MA
authors: De Robertis
authors: Cedars-Sinai Heart Institute, Los Angeles, California.|Capricor Inc., Los Angeles, California.
authors: Linda
authors: L
authors: Marbán
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Lawrence S C
authors: LSC
authors: Czer
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Alfredo
authors: A
authors: Trento
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Eduardo
authors: E
authors: Marbán
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D009202:Cardiomyopathies / Q000503:physiopathology; D005109:Extracellular Matrix; D005260:Female; D006085:Graft Survival / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D016513:Mice, SCID; D008875:Middle Aged; D009203:Myocardial Infarction / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000502:physiology*; D014182:Transplantation, Autologous
chemical_list: D036341:Intercellular Signaling Peptides and Proteins