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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4440-4448. Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-09-3079. This Article Full Text (PDF) All Versions of this Article: 2003-09-3079v1 103/12/4440    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gammaitoni, L. Articles by Piacibello, W. Search for Related Content PubMed PubMed Citation Articles by Gammaitoni, L. Articles by Piacibello, W. Social Bookmarking                   What's this? Submitted September 8, 2003 Accepted January 6, 2004 Elevated telomerase activity, minimal telomere loss in cord blood long-term cultures with extensive stem cell replication Loretta Gammaitoni, Katja C Weisel, Monica Gunetti, Kai-Da Wu, Stefania Bruno, Silvana Pinelli, Antonio Bonati, Massimo Aglietta, Malcolm A Moore, and Wanda Piacibello* Division of Clinical Oncology, IRCC Istitute for Cancer Research and Treatment, Candiolo, Torino, Italy James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Department of Clinical Sciences, Section of Hematology/Oncology, University of Parma Medical School, Parma, Italy * Corresponding author; email: wanda.piacibello{at}ircc.it. 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 Tpo, or stimulated by a cytokine cocktail in the absence of stroma, with, in one method, CD34+ cells re-isolated 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 18-20 weeks and by SCID Repopulating Cells (SRC), capable of repopulating and serially passage in NOD/SCID mice, for 16 weeks. Despite this extensive proliferation, telomere length initially increased and only at late stages of culture was there evidence of telomere shortening. 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 3-4 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. C. Zhang, M. Kaba, S. Iizuka, H. Huynh, and H. F. Lodish Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation Blood, April 1, 2008; 111(7): 3415 - 3423. [Abstract] [Full Text] [PDF] M. Jaras, A. Edqvist, J. Rebetz, L. G. Salford, B. Widegren, and X. Fan Human short-term repopulating cells have enhanced telomerase reverse transcriptase expression Blood, August 1, 2006; 108(3): 1084 - 1091. [Abstract] [Full Text] [PDF]

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