Simonsen Janne L, Rosada Cecilia, Serakinci Nedime, Justesen Jeannette, Stenderup Karin, Rattan Suresh I S, Jensen Thomas G, Kassem Moustapha
Department of Endocrinology and Metabolism, University Hospital of Aarhus, DK-8000 Aarhus C, Denmark.
Nat Biotechnol. 2002 Jun;20(6):592-6. doi: 10.1038/nbt0602-592.
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.
人骨髓基质细胞（hMSCs）通过含有人类端粒酶催化亚基（hTERT）基因的逆转录病毒载体进行稳定转导。转导后的细胞（hMSC-TERTs）具有端粒酶活性，与对照细胞相比，平均端粒长度增加。转导后的细胞现已经历了超过260次群体倍增（PD）并继续增殖，而对照细胞在26次PD后经历了与衰老相关的增殖停滞。在连续传代培养过程中，这些细胞保持成骨细胞标志物的产生和分化潜能，不形成肿瘤，并且具有正常的核型。当皮下植入免疫缺陷小鼠时，转导后的细胞比正常细胞形成更多的骨。这些结果表明，hMSCs中端粒酶的异位表达可防止与衰老相关的成骨细胞功能损伤。
