Bone formation by human postnatal bone marrow stromal stem cells is
enhanced by telomerase expression
Songtao Shi1, 5, Stan Gronthos1, 2, 5, Shaoqiong Chen3, Anand Reddi3, Christopher M. Counter4, Pamela G. Robey1
& Cun-Yu Wang3
1
Craniofacial and Skeletal Diseases Branch,
National Institute of Dental and Craniofacial Research, National Institutes of
Health, Bethesda, MD 20892.
2
Current address: Division of Haematology,
Institute of Medical and Veterinary Science, Frome Road,
Adelaide 5000 South Australia,
Australia.
3
Laboratory of Molecular Signaling and Apoptosis,
Department of Biologic and Materials Sciences, School of Dentistry, University
of Michigan, Ann Arbor, MI 48109.
4
Department of Medicine, Duke University Medical
Center, Durham, NC 27710.
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 pre-osteogenic stem cell marker
STRO-1, indicating that telomerase expression helped to maintain the osteogenic
stem cell pool during ex vivo 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.
