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Stem Cells International
Volume 2017, Article ID 4790563, 9 pages
Research Article

Sex Differences of Human Cardiac Progenitor Cells in the Biological Response to TNF-α Treatment

1Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Rome, Italy
2Department of Medical Surgical Sciences and Biotechnologies, “La Sapienza” University of Rome, Rome, Italy
3Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00185 Rome, Italy
4Malzoni Clinical-Scientific Institute (MaCSI), Via Carmelo Errico 2, 83100 Avellino, Italy
5Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy

Correspondence should be addressed to Elisabetta Straface; ti.ssi@ecafarts.attebasile

Received 23 February 2017; Revised 9 June 2017; Accepted 14 June 2017; Published 17 September 2017

Academic Editor: Leonard M. Eisenberg

Copyright © 2017 Elisabetta Straface et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Adult cardiac progenitor cells (CPCs), isolated as cardiosphere-derived cells (CDCs), represent promising candidates for cardiac regenerative therapy. CDCs can be expanded in vitro manyfolds without losing their differentiation potential, reaching numbers that are appropriate for clinical applications. Since mechanisms of successful CDC survival and engraftment in the damaged myocardium are still critical and unresolved issues, we aimed at deciphering possible key factors capable of bolstering CDC function. In particular, the response and the phenotype of CDCs exposed to low concentrations of the multifunctional cytokine tumor necrosis factor α (TNF-α), known to be capable of activating cell survival pathways, have been investigated. Furthermore, differential biological responses of CDCs from male and female donors, in terms of cell cycle progression and cell spreading, have also been assessed. The results obtained indicate that (i) the intracellular signaling activated in our experimental conditions is most likely due to the prosurvival and proliferative signaling of TNF-α receptor 2 and that (ii) cells from female patients appear more responsive to TNF-α treatment in terms of cell cycle progression and migration ability. In conclusion, the present report highlights the hypothesis that TNF-stimulated CDCs isolated from females may represent a promising candidate for cardiac regenerative therapy applications.