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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 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 Citation Map 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. Related Collections Hematopoiesis and Stem Cells Transplantation Cell Cycle Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Elevated telomerase activity and 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. S. Moore, and Wanda Piacibello From the Laboratory of Clinical Oncology, IRCC—Institute for Cancer Research and Treatment, Torino, Italy; James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Department of Clinical Sciences, Section of Hemato-Oncology, University of Parma Medical School, Parma, Italy. 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. (Blood. 2004;103:4440-4448) 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. W. Drummond, S. Balabanov, T. L. Holyoake, and T. H. Brummendorf Concise Review: Telomere Biology in Normal and Leukemic Hematopoietic Stem Cells Stem Cells, August 1, 2007; 25(8): 1853 - 1861. [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] L. Gammaitoni, S. Lucchi, S. Bruno, M. Tesio, M. Gunetti, Y. Pignochino, G. Migliardi, L. Lazzari, M. Aglietta, P. Rebulla, et al. Serial Transplantations in Nonobese Diabetic/Severe Combined Immunodeficiency Mice of Transduced Human CD34+ Cord Blood Cells: Efficient Oncoretroviral Gene Transfer and Ex Vivo Expansion Under Serum-Free Conditions Stem Cells, May 1, 2006; 24(5): 1201 - 1212. [Abstract] [Full Text] [PDF] S. M. Majka, M. A. Beutz, M. Hagen, A. A. Izzo, N. Voelkel, and K. M. Helm Identification of Novel Resident Pulmonary Stem Cells: Form and Function of the Lung Side Population Stem Cells, September 1, 2005; 23(8): 1073 - 1081. [Abstract] [Full Text] [PDF]

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