Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication

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Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication. / Gammaitoni, Loretta; Weisel, Katja C; Gunetti, Monica; Wu, Kai-Da; Bruno, Stefania; Pinelli, Silvana; Bonati, Antonio; Aglietta, Massimo; Moore, Malcolm A S; Piacibello, Wanda.

in: BLOOD, Jahrgang 103, Nr. 12, 15.06.2004, S. 4440-8.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Gammaitoni, L, Weisel, KC, Gunetti, M, Wu, K-D, Bruno, S, Pinelli, S, Bonati, A, Aglietta, M, Moore, MAS & Piacibello, W 2004, 'Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication', BLOOD, Jg. 103, Nr. 12, S. 4440-8. https://doi.org/10.1182/blood-2003-09-3079

APA

Gammaitoni, L., Weisel, K. C., Gunetti, M., Wu, K-D., Bruno, S., Pinelli, S., Bonati, A., Aglietta, M., Moore, M. A. S., & Piacibello, W. (2004). Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication. BLOOD, 103(12), 4440-8. https://doi.org/10.1182/blood-2003-09-3079

Vancouver

Bibtex

@article{add4fc8aac6c4306a7ec08389605bc5a,
title = "Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication",
abstract = "Telomerase activity, telomere length, stem/progenitor cell production, and function of CD34+ cells from cord blood (CB), bone marrow, and mobilized peripheral blood were evaluated in long-term cultures. CB cells were cultured either on OP-9 stromal cells transduced with an adenovector expressing thrombopoietin (TPO) or stimulated by a cytokine cocktail in the absence of stroma, with, in one method, CD34+ cells reisolated at monthly intervals for passage. Continuous expansion of stem cells as measured by in vitro cobblestone area and secondary colony-forming assays was noted for 18 to 20 weeks and by severe combined immunodeficiency (SCID)-repopulating cells (SRCs), capable of repopulating and serially passage in nonobese diabetic/SCID mice, for 16 weeks. Despite this extensive proliferation, telomere length initially increased and only at late stages of culture was evidence of telomere shortening noted. This telomere stabilization correlated with maintenance of high levels of telomerase activity in the CD34+ cell population for prolonged periods of culture. Cytokine-stimulated cultures of adult CD34+ cells showed CD34+ and SRC expansion (6-fold) for only 3 to 4 weeks with telomere shortening and low levels of telomerase. There is clearly a clinical value for a system that provides extensive stem cell expansion without concomitant telomere erosion.",
keywords = "Adenoviridae, Animals, Antigens, CD, Antigens, CD34, Cell Division, Fetal Blood, Genetic Vectors, Hematopoietic Stem Cells, Humans, Infant, Newborn, Mice, Mice, Inbred NOD, Mice, SCID, Telomerase, Thrombopoietin, Transfection, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.",
author = "Loretta Gammaitoni and Weisel, {Katja C} and Monica Gunetti and Kai-Da Wu and Stefania Bruno and Silvana Pinelli and Antonio Bonati and Massimo Aglietta and Moore, {Malcolm A S} and Wanda Piacibello",
year = "2004",
month = jun,
day = "15",
doi = "10.1182/blood-2003-09-3079",
language = "English",
volume = "103",
pages = "4440--8",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "12",

}

RIS

TY - JOUR

T1 - Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication

AU - Gammaitoni, Loretta

AU - Weisel, Katja C

AU - Gunetti, Monica

AU - Wu, Kai-Da

AU - Bruno, Stefania

AU - Pinelli, Silvana

AU - Bonati, Antonio

AU - Aglietta, Massimo

AU - Moore, Malcolm A S

AU - Piacibello, Wanda

PY - 2004/6/15

Y1 - 2004/6/15

N2 - Telomerase activity, telomere length, stem/progenitor cell production, and function of CD34+ cells from cord blood (CB), bone marrow, and mobilized peripheral blood were evaluated in long-term cultures. CB cells were cultured either on OP-9 stromal cells transduced with an adenovector expressing thrombopoietin (TPO) or stimulated by a cytokine cocktail in the absence of stroma, with, in one method, CD34+ cells reisolated at monthly intervals for passage. Continuous expansion of stem cells as measured by in vitro cobblestone area and secondary colony-forming assays was noted for 18 to 20 weeks and by severe combined immunodeficiency (SCID)-repopulating cells (SRCs), capable of repopulating and serially passage in nonobese diabetic/SCID mice, for 16 weeks. Despite this extensive proliferation, telomere length initially increased and only at late stages of culture was evidence of telomere shortening noted. This telomere stabilization correlated with maintenance of high levels of telomerase activity in the CD34+ cell population for prolonged periods of culture. Cytokine-stimulated cultures of adult CD34+ cells showed CD34+ and SRC expansion (6-fold) for only 3 to 4 weeks with telomere shortening and low levels of telomerase. There is clearly a clinical value for a system that provides extensive stem cell expansion without concomitant telomere erosion.

AB - Telomerase activity, telomere length, stem/progenitor cell production, and function of CD34+ cells from cord blood (CB), bone marrow, and mobilized peripheral blood were evaluated in long-term cultures. CB cells were cultured either on OP-9 stromal cells transduced with an adenovector expressing thrombopoietin (TPO) or stimulated by a cytokine cocktail in the absence of stroma, with, in one method, CD34+ cells reisolated at monthly intervals for passage. Continuous expansion of stem cells as measured by in vitro cobblestone area and secondary colony-forming assays was noted for 18 to 20 weeks and by severe combined immunodeficiency (SCID)-repopulating cells (SRCs), capable of repopulating and serially passage in nonobese diabetic/SCID mice, for 16 weeks. Despite this extensive proliferation, telomere length initially increased and only at late stages of culture was evidence of telomere shortening noted. This telomere stabilization correlated with maintenance of high levels of telomerase activity in the CD34+ cell population for prolonged periods of culture. Cytokine-stimulated cultures of adult CD34+ cells showed CD34+ and SRC expansion (6-fold) for only 3 to 4 weeks with telomere shortening and low levels of telomerase. There is clearly a clinical value for a system that provides extensive stem cell expansion without concomitant telomere erosion.

KW - Adenoviridae

KW - Animals

KW - Antigens, CD

KW - Antigens, CD34

KW - Cell Division

KW - Fetal Blood

KW - Genetic Vectors

KW - Hematopoietic Stem Cells

KW - Humans

KW - Infant, Newborn

KW - Mice

KW - Mice, Inbred NOD

KW - Mice, SCID

KW - Telomerase

KW - Thrombopoietin

KW - Transfection

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, P.H.S.

U2 - 10.1182/blood-2003-09-3079

DO - 10.1182/blood-2003-09-3079

M3 - SCORING: Journal article

C2 - 14726371

VL - 103

SP - 4440

EP - 4448

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 12

ER -