Effects of telomerase modulation in human hematopoietic progenitor cells

Stem Cells
Stefan ZimmermannUwe M Martens

Abstract

Loss of telomeric repeats has been causally linked to replicative senescence and aging in human cells. In contrast to normal somatic cells, which are telomerase-negative, hematopoietic stem cells have low levels of telomerase, which can be transiently upregulated upon cytokine stimulation. To examine whether ectopic expression of telomerase can overcome telomere erosion in hematopoietic progenitor cells, we overexpressed telomerase in CD34+ and AC133+ cord blood (CB) cells using retroviral vectors containing hTERT, the catalytic component of telomerase. Although the hTERT-transduced CB cells exhibited significantly elevated telomerase activity (approximately 10-fold), the mean telomere length was only increased up to 600 bp, which was in contrast to hTERT-transduced fibroblast cells gaining more than 2-kb telomeric repeats. Moreover, ectopic telomerase activity did not prevent overall telomere shortening, which was in the range of 1.3 kb in serum-free expansion culture. We also blocked endogenous telomerase activity by ectopic expression of dominant-negative hTERT. Whereas CB cells with absent telomerase activity showed reduced absolute numbers of colony-forming cells, we observed increased rates only for burst-forming units er...Continue Reading

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Citations

Nov 26, 2009·European Journal of Clinical Pharmacology·Meng DongUlrich Klotz
Oct 26, 2007·Cell and Tissue Research·Stefan Zimmermann, Uwe M Martens
Mar 4, 2010·Tissue Engineering. Part B, Reviews·Wolfgang WagnerMartin Zenke
Oct 27, 2009·Tissue Engineering. Part C, Methods·Tatsuya MimuraShiro Amano
Sep 15, 2010·Rheumatology·Inés Colmegna, Cornelia M Weyand
Feb 24, 2005·Artificial Organs·Anton WernigStefan Zimmermann
May 15, 2010·Future Oncology·Michelle F MaritzKaren L MacKenzie
Sep 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·J C Y WangJ E Dick
Jan 29, 2013·Progress in Retinal and Eye Research·Tatsuya MimuraShiro Amano
Jul 16, 2008·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·F Mathias Bollmann
Jan 10, 2009·Proteomics·Stefan ZimmermannUwe M Martens
Nov 13, 2008·International Journal of Cancer. Journal International Du Cancer·Udo SieboltsClaudia Wickenhauser
Mar 6, 2008·Journal of Cellular and Molecular Medicine·Wolfgang BöckerMatthias Schieker
Apr 29, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Zhenyu Ju, Karl Lenhard Rudolph
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Jul 17, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carlos SebastiánAntonio Celada

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