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

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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Figure 1: Presence of ectopic hTERT in hMSC-TERTs.
Figure 2: Effect of hTERT expression on life-span of hMSC-TERTs.
Figure 3: In vivo bone formation by hMSC-TERTs.
Figure 4: Comparative genomic hybridization on hMSC-TERTs.

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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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Correspondence to Moustapha Kassem.

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Simonsen, J., Rosada, C., Serakinci, N. et al. Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nat Biotechnol 20, 592–596 (2002). https://doi.org/10.1038/nbt0602-592

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