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Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells

Nature Biotechnology volume 20, pages 592596 (2002) | Download Citation

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Abstract

Human bone marrow stromal cells (hMSCs) were stably transduced by a retroviral vector containing the gene for the catalytic subunit of human telomerase (hTERT). Transduced cells (hMSC-TERTs) had telomerase activity, and the mean telomere length was increased as compared with that of control cells. The transduced cells have now undergone more than 260 population doublings (PD) and continue to proliferate, whereas control cells underwent senescence-associated proliferation arrest after 26 PD. The cells maintained production of osteoblastic markers and differentiation potential during continuous subculturing, did not form tumors, and had a normal karyotype. When implanted subcutaneously in immunodeficient mice, the transduced cells formed more bone than did normal cells. These results suggest that ectopic expression of telomerase in hMSCs prevents senescence-associated impairment of osteoblast functions.

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Acknowledgements

We thank Claus Bischoff, Frederik Dagnaes-Hansen, Tamer Al-Soubeky, Erik F. Eriksen, Flemming Melsen, Lotte Sørensen, Anette Baatrup, Jette Barlach, Thrine Schneidermann, and Anne Keblovszki for their advice and technical assistance. This work was supported by grants from the Danish Medical Research Council, the Danish Centre for Molecular Gerontology, and the Novo Nordisk Foundation.

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Author notes

    • Janne L. Simonsen
    •  & Cecilia Rosada

    These authors contributed equally to this work.

Affiliations

  1. Department of Endocrinology and Metabolism, University Hospital of Aarhus, DK-8000 Aarhus C, Denmark.

    • Janne L. Simonsen
    • , Cecilia Rosada
    • , Jeannette Justesen
    • , Karin Stenderup
    •  & Moustapha Kassem
  2. Cancer Cytogenetics Laboratory, University Hospital of Aarhus, DK-8000 Aarhus C, Denmark.

    • Nedime Serakinci
  3. Danish Centre for Molecular Gerontology, Department of Molecular and Structural Biology, University of Aarhus, DK-8000 Aarhus C, Denmark.

    • Suresh I.S. Rattan
  4. Department of Human Genetics, University of Aarhus, DK-8000 Aarhus C, Denmark.

    • Nedime Serakinci
    •  & Thomas G. Jensen
  5. Department of Endocrinology and Metabolism, University Hospital of Odense, DK-5000 Odense C, Denmark.

    • Janne L. Simonsen
    • , Cecilia Rosada
    • , Jeannette Justesen
    • , Karin Stenderup
    •  & Moustapha Kassem

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The authors declare no competing financial interests.

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Correspondence to Moustapha Kassem.

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DOI

https://doi.org/10.1038/nbt0602-592

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