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Human Cardiosphere-Derived Cells From Advanced Heart Failure Patients Exhibit Augmented Functional Potency in Myocardial Repair.
MedLine Citation:
PMID:  24511463     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVES: 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 1 (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:
Ke Cheng; Konstantinos Malliaras; Rachel Ruckdeschel Smith; Deliang Shen; Baiming Sun; Agnieszka Blusztajn; Yucai Xie; Ahmed Ibrahim; Mohammad Amin Aminzadeh; Weixin Liu; Tao-Sheng Li; Michele A De Robertis; Linda Marbán; Lawrence S C Czer; Alfredo Trento; Eduardo Marbán
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Publication Detail:
Type:  JOURNAL ARTICLE    
Journal Detail:
Title:  JACC. Heart failure     Volume:  2     ISSN:  2213-1779     ISO Abbreviation:  JACC Heart Fail     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-2-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101598241     Medline TA:  JACC Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  49-61     Citation Subset:  -    
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