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

Elisabetta Straface, Lucrezia Gambardella, Francesca Pagano, Francesco Angelini, Barbara Ascione, Rosa Vona, Elena De Falco, Elena Cavarretta, Raffaele La Russa, Walter Malorni, Giacomo Frati, Isotta Chimenti

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)4790563
JournalStem Cells International
Volume2017
DOIs
Publication statusPublished - 2017

Fingerprint

Sex Characteristics
Stem Cells
Tumor Necrosis Factor-alpha
Therapeutics
Cell Survival
Cell Cycle
Receptors, Tumor Necrosis Factor, Type II
Cell Movement
Myocardium
Tissue Donors
Cytokines
Phenotype

Keywords

  • Gender differences
  • Sex differences

Cite this

Sex Differences of Human Cardiac Progenitor Cells in the Biological Response to TNF-Treatment. / Straface, Elisabetta; Gambardella, Lucrezia; Pagano, Francesca; Angelini, Francesco; Ascione, Barbara; Vona, Rosa; De Falco, Elena; Cavarretta, Elena; Russa, Raffaele La; Malorni, Walter; Frati, Giacomo; Chimenti, Isotta.

In: Stem Cells International, Vol. 2017, 2017, p. 4790563.

Research output: Contribution to journalArticle

Straface, Elisabetta ; Gambardella, Lucrezia ; Pagano, Francesca ; Angelini, Francesco ; Ascione, Barbara ; Vona, Rosa ; De Falco, Elena ; Cavarretta, Elena ; Russa, Raffaele La ; Malorni, Walter ; Frati, Giacomo ; Chimenti, Isotta. / Sex Differences of Human Cardiac Progenitor Cells in the Biological Response to TNF-Treatment. In: Stem Cells International. 2017 ; Vol. 2017. pp. 4790563.
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abstract = "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.",
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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

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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.

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