Abstract 20223: Deep Proteome Analysis Identified Complete Secretome as the Functional Unit of Human Cardiac Progenitor Cells
This investigation determines how chronological age influences the phenotypic characteristics and the secretome of human c-kit+ cardiac progenitor cells (CPCs) when comparing adult CPCs (aCPCs, age > 40 years) to neonatal CPCs (nCPCs, age < 1 month). The stronger growth characteristics of the in vitro expanded nCPCs correlated with significant myocardial recovery in the myocardial infarction (MI) rodent model when compared to aCPCs. Strikingly, a single injection of nCPCs-total conditioned media (TCM) was significantly more effective than injected nCPCs, aTCM, or exosomes derived from nCPCs for recovering cardiac function, stimulating neovascularization, and promoting myocardial remodeling after MI. Using LC MS/MS, we quantified changes of 897 proteins in nTCM and 524 proteins in aTCM. To interpret these protein databases, we used a literature based networking software which identified a total 46 canonical pathways. This approach suggested that the heat shock proteins significantly affected 8 of these pathways and the heat shock factor-1 (HSF-1) is among the key regulators of these pathway. Validating this prediction, we demonstrated that inhibition of HSF-1 expression in nCPCs significantly reduced the amount of secretome essential for cardiovascular regeneration. In conclusion, deep proteomic analysis revealed both detailed and global mechanisms that contribute to CPC’s functional activity affected by chronological aging.
Author Disclosures: S. Sharma: None. R. Mishra: None. G.E. Bigham: None. B.P. Wehman: None. M.M. Khan: None. S. Datla: None. P. Saha: None. Y.A. Goo: None. L. Chen: None. D.R. Goodlett: None. S. Kaushal: None.
- © 2016 by American Heart Association, Inc.