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

TY - JOUR

T1 - Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells

AU - Simonsen, Janne Lytoft

AU - Rosada, Cecilia

AU - Serakinci, Nedime

AU - Justesen, Jeannette

AU - Stenderup, Karin

AU - Rattan, Suresh

AU - Jensen, Thomas G.

AU - Kassem, Moustapha

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

U2 - 10.1038/nbt0602-592

DO - 10.1038/nbt0602-592

M3 - Journal article

C2 - 12042863

SN - 1087-0156

VL - 20

SP - 592

EP - 596

JO - Nature Biotechnology

JF - Nature Biotechnology

IS - 6

ER -