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

• Published in: Nature biotechnology Vol. 20; no. 6; pp. 587 - 591
• Main Authors: Wang, Cun-Yu, Shi, Songtao, Gronthos, Stan, Chen, Shaoqiong, Reddi, Anand, Counter, Christopher M, Robey, Pamela G
• Format: Journal Article
• Language: English
• Published: New York, NY Nature 01.06.2002; Nature Publishing Group
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Applied cell therapy and gene therapy; Biological and medical sciences; Biotechnology; Bone marrow; Bone Remodeling - genetics; Bone Remodeling - physiology; Cell Differentiation - genetics; DNA-Binding Proteins; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression Regulation, Developmental - physiology; Gene therapy; Health. Pharmaceutical industry; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Humans; Industrial applications and implications. Economical aspects; Medical sciences; Mice; Osteogenesis - genetics; Osteogenesis - physiology; Reference Values; Stem cells; Stromal Cells - physiology; Stromal Cells - transplantation; Telomerase - genetics; Tissue Engineering - methods; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Heterologous; Human; Cell proliferation; Cell culture; Cell therapy; Enzyme; Stem cell; Transplantation; Longevity; Gene expression; Postnatal; Ex vivo; Bone marrow; Stromal cell; Bone; Repair; Gene therapy; Telomerase; Osteogenesis
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt0602-587

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.