TY - JOUR
T1 - Sex Differences of Human Cardiac Progenitor Cells in the Biological Response to TNF-Treatment
AU - Straface, Elisabetta
AU - Gambardella, Lucrezia
AU - Pagano, Francesca
AU - Angelini, Francesco
AU - Ascione, Barbara
AU - Vona, Rosa
AU - De Falco, Elena
AU - Cavarretta, Elena
AU - Russa, Raffaele La
AU - Malorni, Walter
AU - Frati, Giacomo
AU - Chimenti, Isotta
PY - 2017
Y1 - 2017
N2 - 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 factorα(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-αreceptor 2 and that (ii) cells from female patients appear more responsive to TNF-αtreatment 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.
AB - 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 factorα(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-αreceptor 2 and that (ii) cells from female patients appear more responsive to TNF-αtreatment 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.
KW - Gender differences
KW - Sex differences
U2 - 10.1155/2017/4790563
DO - 10.1155/2017/4790563
M3 - Article
C2 - 29104594
VL - 2017
SP - 4790563
JO - Stem Cells International
JF - Stem Cells International
SN - 1687-966X
ER -