Relevance and Safety of Telomerase for Human Tissue Engineering

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 ectopi...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2006-02, Vol.103 (8), p.2500-2505
Hauptverfasser: Klinger, Rebecca Y., Blum, Juliana L., Hearn, Bevin, Lebow, Benjamin, Niklason, Laura E.
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container_issue 8
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container_title Proceedings of the National Academy of Sciences - PNAS
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creator Klinger, Rebecca Y.
Blum, Juliana L.
Hearn, Bevin
Lebow, Benjamin
Niklason, Laura E.
description 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 upregulation 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.
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subjects Biological Sciences
Blood Vessels - cytology
Blood Vessels - enzymology
Blood Vessels - physiology
Cell culture techniques
Cell Culture Techniques - methods
Cell growth
Cell Transformation, Neoplastic
Cellular senescence
Chromosome Aberrations
Cultured cells
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Endothelial cells
Humans
Karyotype
Mesenchymal stem cells
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - enzymology
Muscle, Smooth, Vascular - physiology
Myocytes, Smooth Muscle - cytology
Myocytes, Smooth Muscle - enzymology
Myocytes, Smooth Muscle - physiology
Older adults
Retroviridae - genetics
Telomerase - genetics
Telomerase - metabolism
Telomere - enzymology
Telomere - genetics
Tissue engineering
Tissue Engineering - methods
Tissue Engineering Special Feature
Transfection
Tumors
title Relevance and Safety of Telomerase for Human Tissue Engineering
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