TY - JOUR
T1 - Influence of Donor and Recipient Gender on Telomere Maintenance after Umbilical Cord Blood Cell Transplantation
T2 - A Study by the Gruppo Italiano Trapianto Di Midollo Osseo
AU - Derenzini, Enrico
AU - Risso, Alessandra
AU - Ruella, M.
AU - Spatola, Tiziana
AU - Milone, Giuseppe
AU - Pioltelli, Pietro
AU - Iori, Anna Paola
AU - Santarone, Stella
AU - Bosi, Alberto
AU - Rambaldi, Alessandro
AU - Bacigalupo, Andrea P.
AU - Arcese, William
AU - Tarella, Corrado
PY - 2019/7
Y1 - 2019/7
N2 - Physiologic loss of telomerase activity in adult life determines progressive telomere length (TL) shortening. Inflammation and oxidative damage are established causes of TL loss; moreover, males have shorter telomeres compared with females. Despite these notions, mechanisms regulating TL maintenance are poorly defined. Because umbilical cord blood (UCB) cells harbor very long telomeres, not yet exposed to environmental damages, UCB transplantation (UCBT) provides a unique experimental setting to study determinants of TL in humans. TL dynamics were analyzed on peripheral blood mononuclear cells (MNCs) from 36 patients (median age, 42 years) undergoing UCBT. TL was studied at a median of 20 months after UCBT. A significantly longer TL (mean, 8698 bp; range, 6521 to 11,960) was documented in UCBT recipients compared with age-matched healthy control subjects (mean, 7396 bp; range, 4375 to 11,108; P < .01). Among variables potentially influencing TL maintenance, including recipient features, graft type, transplant procedure, and engraftment kinetics, only donor–recipient gender combination was associated with TL, with the longest TL in women receiving male UCB (mean, 10,063 bp; range, 8381 to 11,960). To further investigate this trend, telomerase activation was assessed in vitro. Experiments showed that telomerase subunits were preferentially upregulated in male-derived bone marrow MNCs exposed ex vivo to estradiol as compared with female MNCs. This implies an increased sensitivity of male-derived MNCs to telomerase activation induced by estradiol. The results suggest that extrinsic and modifiable factors such as hormonal status and female milieu could be major determinants of TL in humans, providing the rationale for investigating hormonal-based approaches to counteract telomere erosion and aging-related diseases.
AB - Physiologic loss of telomerase activity in adult life determines progressive telomere length (TL) shortening. Inflammation and oxidative damage are established causes of TL loss; moreover, males have shorter telomeres compared with females. Despite these notions, mechanisms regulating TL maintenance are poorly defined. Because umbilical cord blood (UCB) cells harbor very long telomeres, not yet exposed to environmental damages, UCB transplantation (UCBT) provides a unique experimental setting to study determinants of TL in humans. TL dynamics were analyzed on peripheral blood mononuclear cells (MNCs) from 36 patients (median age, 42 years) undergoing UCBT. TL was studied at a median of 20 months after UCBT. A significantly longer TL (mean, 8698 bp; range, 6521 to 11,960) was documented in UCBT recipients compared with age-matched healthy control subjects (mean, 7396 bp; range, 4375 to 11,108; P < .01). Among variables potentially influencing TL maintenance, including recipient features, graft type, transplant procedure, and engraftment kinetics, only donor–recipient gender combination was associated with TL, with the longest TL in women receiving male UCB (mean, 10,063 bp; range, 8381 to 11,960). To further investigate this trend, telomerase activation was assessed in vitro. Experiments showed that telomerase subunits were preferentially upregulated in male-derived bone marrow MNCs exposed ex vivo to estradiol as compared with female MNCs. This implies an increased sensitivity of male-derived MNCs to telomerase activation induced by estradiol. The results suggest that extrinsic and modifiable factors such as hormonal status and female milieu could be major determinants of TL in humans, providing the rationale for investigating hormonal-based approaches to counteract telomere erosion and aging-related diseases.
KW - Aging
KW - Cord blood transplantation
KW - Estradiol
KW - Hematopoiesis
KW - Telomerase
KW - Telomere length
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U2 - 10.1016/j.bbmt.2019.03.026
DO - 10.1016/j.bbmt.2019.03.026
M3 - Article
C2 - 30935966
AN - SCOPUS:85065392396
VL - 25
SP - 1387
EP - 1394
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 7
ER -