Abstract 19286: Human Cardiac Progenitors Isolated From Young Donors Harbor a Less Mature Phenotype Compared to Progenitors From Adult Donors
Introduction: Resident cardiac progenitor populations induce regeneration after myocardial infarction. Here we compare c-kitpos cardiac progenitor cells (CPC) and cardiosphere-derived cells (CDC) to examine the effect of donor age (young (Y) vs. adult (A) human hearts) on cardiomyocyte (CM) and endothelial cell (EC) differentiation and paracrine factor release.
Methods: Right atrial appendage surgical biopsies from Y (3d-14y old) and A (47-84y old) patients were digested and expanded in vitro. Following c-kit antigen selection (c-kitpos CPC; Y, n=10; A, n=12) or explant outgrowth (CDC; Y, n=7; A, n=9), cells were characterized by RNA-sequencing (NextSeq500, Illumina, 3-7 million reads/sample, significance set at 2-fold change), qRT-PCR, flow cytometry and population doubling times (PDT). Progenitor differentiation towards EC was measured using 2D and 3D matrigel tube formation assays (24h) and CM differentiation was assessed by alpha-sarcomeric actinin (aSA) positivity (12d). Growth factor release in 48h serum-free conditioned medium was analyzed by ELISA.
Results: IPA analysis showed higher activation of cell cycle pathways, eNOS signaling and immunomodulatory pathways in aCDC than in yCDC and c-kitpos CPC, all of which may contribute to a reparative or cardioprotective phenotype. c-Kit expression was increased in c-kitpos CPC compared to CDC (P<0.01). CD105 expression was increased in aCDC (P<0.001 vs. yCDC) but CD90 expression was lower (P<0.001 vs. yCDC or c-kitpos CPC). Lineage marker transcripts (CD31, MEF2c, GATA4) were significantly elevated in aCDC (P<0.05 vs. yCDC and c-kitpos CPC). PDT in a CDC and c-kitpos yCPC were significantly shorter than in their age-matched counterparts (P<0.02). We observed more firmly established networks in 2D and 3D matrigel and elevated secretion of pro-angiogenic and cytoprotective IGF-1, HGF, bFGF, VEGF, PlGF and SDF-1 in aCDC than in yCDC and c-kitpos CPC. aCPC have superior CM differentiation potential than yCPC and yCDC or aCDC (aSA+, P<0.05).
Conclusions: aCDC have a superior autocrine and paracrine pro-angiogenic profile while adult c-kitpos CPC have greater cardiomyogenic potential. Combination strategies of adult-derived resident cardiac progenitors warrant clinical translation.
Author Disclosures: A. Walravens: None. L. Ottaviani: None. M. Vanhaverbeke: None. H. Gillijns: None. N. Vanden Driessche: None. S. Trenson: None. A. Luttun: None. J. Voigt: None. B. Meyns: None. P. Herijgers: None. F. Rega: None. B. Meuris: None. R. Heying: None. M. Sampaolesi: None. S. Janssens: None.
- © 2016 by American Heart Association, Inc.