Nature Biotechnology
20, 592 - 596 (2002)
doi:10.1038/nbt0602-592
Telomerase expression extends the proliferative life-span and
maintains the osteogenic potential of human bone marrow stromal cellsJanne L. Simonsen1, 5, 6, Cecilia Rosada1, 5, 6, Nedime Serakinci2, 4, Jeannette Justesen1, 5, Karin Stenderup1, 5, Suresh I.S. Rattan3, Thomas G. Jensen4
& Moustapha Kassem1, 51
Department of Endocrinology and Metabolism,
University Hospital of Aarhus, DK-8000 Aarhus C,
Denmark. 2
Cancer Cytogenetics Laboratory, University
Hospital of Aarhus, DK-8000 Aarhus C,
Denmark. 3
Danish Centre for Molecular Gerontology,
Department of Molecular and Structural Biology, University of Aarhus,
DK-8000 Aarhus C, Denmark. 4
Department of Human Genetics, University of
Aarhus, DK-8000 Aarhus C, Denmark. 5
Department of Endocrinology and Metabolism,
University Hospital of Odense, DK-5000 Odense C,
Denmark. 6
These authors contributed equally to this work.
Correspondence should be addressed to Moustapha Kassem mkassem@dadlnet.dkHuman 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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