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

Nature Biotechnology volume 20, pages 587–591 (2002)Cite this article

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 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.

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Figure 1: Ectopic expression of hTERT induces telomerase activity in BMSSCs.
Figure 2: Telomerase expression enhances osteoblast differentiation in vitro.
Figure 3: Histological characterization of regenerated bone by transplantation of BMSSC-Ts at PD20 and BMSSC-Cs at PD20 in vivo.
Figure 4: Telomerase expression extends bone-forming capacity of BMSSCs in vivo.
Figure 5: Telomerase expression enhances and maintains STRO-1 expression in BMSSCs.

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Acknowledgements

We thank R. Weinberg for providing plasmids. This work was supported by research grants from the National Institutes of Health (National Institute of Dental and Craniofacial Research) to C.-Y. Wang.

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Author notes

  1. Stan Gronthos

    Present address: Division of Haematology, Institute of Medical and Veterinary Science, Frome Road, Adelaide, 5000, South Australia, Australia

  2. Songtao Shi and Stan Gronthos: These authors contributed equally to this work.

Authors and Affiliations

  1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, 20892, MD

    Songtao Shi, Stan Gronthos & Pamela G. Robey

  2. Laboratory of Molecular Signaling and Apoptosis Department of Biologic and Materials Sciences, Laboratory of Molecular Signaling and Apoptosis, School of Dentistry, University of Michigan, Ann Arbor, 48109, MI

    Shaoqiong Chen, Anand Reddi & Cun-Yu Wang

  3. Department of Medicine, Duke University Medical Center, Durham, 27710, NC

    Christopher M. Counter

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Correspondence to Cun-Yu Wang.

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Shi, S., Gronthos, S., Chen, S. et al. Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression. Nat Biotechnol 20, 587–591 (2002). https://doi.org/10.1038/nbt0602-587

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