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Secreted growth factors from human epicardial‐derived precursor cells protect against progressive injury after myocardial ischemia with reperfusion by preventing vascular rhexis
Author(s) -
Spees Jeffrey L
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.209.1
Subject(s) - paracrine signalling , reperfusion injury , ischemia , myocardial infarction , progenitor cell , medicine , cardiology , pharmacology , infarction , stem cell , microbiology and biotechnology , biology , receptor
Paracrine effects are thought to provide many benefits of cardiac stem/progenitor cell administration, but the key secreted factors and physiological mechanism(s) of their action are poorly understood. Epicardial‐derived precursor cells (EDPCs) support cardiac development, repair and remodeling after injury, in part through paracrine activity. Accordingly, we determined whether factors secreted by human EDPCs into conditioned medium (EPI CdM) would protect jeopardized cardiac tissue after myocardial infarction (MI) with reperfusion. Injection of human EPI CdM markedly reduced infarct size (by 50%) in multiple mouse strains, even after 4 hours of ischemia. Combined depletion of HGF, VEGFA, and SDF‐1 from EPI CdM prior to treatment showed that it protected jeopardized myocardium by preventing the loss of vascular integrity (rhexis) after reperfusion. Our results demonstrate that the paracrine effects of EDPCs are likely to occur through the concerted effects of multiple secreted factors. Based on its ability to protect against vascular rhexis, EPI CdM or a combination of its ligands may provide an effective treatment for acute MI.