Relevance and safety of telomerase for human tissue engineering
Language: 
English
Abstract: 

Tissue engineering holds the promise of replacing damaged or diseased tissues and organs. The use of autologous donor cells is often not feasible because of the limited replicative lifespan of cells, particularly those derived from elderly patients. Proliferative arrest can be overcome by the ectopic expression of telomerase via human telomerase reverse transcriptase (hTERT) gene transfection. To study the efficacy and safety of this potentially valuable technology, we used differentiated vascular smooth muscle cells (SMC) and vascular tissue engineering as a model system. Although we previously demonstrated that vessels engineered with telomerase-expressing SMC had improved mechanics over those grown with control cells, it is critical to assess the phenotypic impact of telomerase expression in donor cells, because telomerase up-regulation is observed in >95% of human malignancies. To study the impact of telomerase in tissue engineering, expression of hTERT was retrovirally induced in SMC from eight elderly patients and one young donor. In hTERT SMC, significant lifespan extension beyond that of control was achieved without population doubling time acceleration. Karyotype changes were seen in both control and hTERT SMC but were not clonal nor representative of cancerous change. hTERT cells also failed to show evidence of neoplastic transformation in functional assays of tumorigenicity. In addition, the impact of donor age on cellular behavior, particularly the synthetic capability of SMC, was not affected by hTERT expression. Hence, this tissue engineering model system highlights the impact of donor age on cellular synthetic function that appears to be independent of lifespan extension by hTERT.

Author(s): 
Klinger, Rebecca Y.
Blum, Juliana L.
Hearn, Bevin
Lebow, Benjamin
Niklason, Laura E.
Item Type: 
Journal Article
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America
Journal Abbreviation: 
Proc. Natl. Acad. Sci. U.S.A.
Publication Date: 
2/21/2006
Publication Year: 
2006
Pages: 
2500-2505
Volume: 
103
Issue: 
8
ISSN: 
0027-8424
DOI: 
10.1073/pnas.0508184103
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 16477025 PMCID: PMC1413782

Turabian/Chicago Citation

Rebecca Y. Klinger, Juliana L. Blum, Bevin Hearn, Benjamin Lebow and Laura E. Niklason. 2/21/2006. "Relevance and safety of telomerase for human tissue engineering." Proceedings of the National Academy of Sciences of the United States of America 103: 8: 2500-2505. 10.1073/pnas.0508184103.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1073/pnas.0508184103 | issn = 0027-8424 | volume = 103 | pages = 2500-2505 | last = Klinger | first = Rebecca Y. | coauthors = Blum, Juliana L., Hearn, Bevin, Lebow, Benjamin, Niklason, Laura E. | title = Relevance and safety of telomerase for human tissue engineering | journal = Proceedings of the National Academy of Sciences of the United States of America | date = 2/21/2006 | pmid = | pmc = }} </ref>