Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression

Shi S.; Gronthos S.; Chen S.; Reddi A.; Counter C.M.; Robey P.G.; Wang C.-Y.

C.-Y. Wang, Laboratory of Molecular Signaling, Department of Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA; e-mail cunywang@umich.edu Abstract

Human postnatal bone marrow stromal stem cells (BMSSCs) have a limited life-span and progressively lose their stem cell properties during ex vivo expansion. Here we report that ectopic expression of human telomerase reverse transcriptase (hTERT) in BMSSCs extended their life-span and maintained their osteogenic potential. In xenogenic transplants, hTERT-expressing BMSSCs (BMSSC-Ts) generated more bone tissue, with a mineralized lamellar bone structure and associated marrow, than did control BMSSCs. The enhanced bone-forming ability of BMSSC-Ts was correlated with a higher and sustained expression of the early preosteogenic stem cell marker STRO-1, indicating that telomerase expression helped to maintain the osteogenic stem cell pool during ex viva expansion. These results show that telomerase expression can overcome critical technical barriers to the ex vivo expansion of BMSSCs, and suggest that telomerase therapy may be a useful strategy for bone regeneration and repair. [Journal Article; 47 Refs; In English; Summary in English]

人骨髓基质干细胞可通过表达端粒酶提高骨形成能力

出生后人骨髓基质干细胞（BMSSCs）寿命有限，在体外扩增过程中渐失其干细胞特征。我们的研究发现人端粒酶逆转录酶（hTERT）的异位表达可延长BMSSCs寿命并维持其成骨潜能。在异种移植中，表达hTERT的BMSSCs比不表达组可产生更多的骨组织，同时伴有矿化的板层骨结构和骨髓形成。BMSSCs骨形成能力的提高与早期成骨干细胞标记STRO-1的持续高表达有相关性，表明在体外扩增过程中端粒酶表达有助于维持“干细胞池”（stem cell pool）。本研究结果显示端粒酶表达可克服BMSSCs体外扩增的关键技术障碍，同时也提示端粒酶疗法可能会成为骨再生、修复中的一种有效途径。

 (Nature Biotechnology, June 2002 Volume 20 Number 6 pp 587 – 591)