Human telomerase reverse transcriptase

Beyond the Hayflick limit, cells that have escaped senescence and/or crisis must progress beyond mortality stage 2 (Figure 26.1). Recent studies have shown that human telomerase reverse transcriptase cDNA (hTERT) in combination with viral oncogenes also has the potential to immortalize human airway epithelial cells [15, 78-82], However, even though hTERT alone will cause enhanced growth potential of a cell line, with the exception of one study [81],... 

F. Bachand and C. Autexier. 2001. Functional regions of human telomerase reverse transcriptase and human telomerase RNA required for telomerase activity and RNA-protein interactions Mo/. Cell Biol. 21 1888-1897. (PuhMed) (Full Text in PMC)... 

Hong HX, Zhang YM, Xu H, Su ZY, and Sun P. Immortalization of swine umbilical vein endothelial cells with human telomerase reverse transcriptase. Mol Cells 24 358-363,2007. 

Kyo S, Takakura M, Taira T, Kanaya T, Itoh H, et al. 2000. Spl cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Res. 28 669-77... 

Dasi F, Lledo S, Garcia-Granero E, RipoU R, Marugan M, Tormo M, et al. Real-time quantification in plasma of human telomerase reverse transcriptase (hTERT) mRNA a simple blood test to monitor disease in cancer patients. Lab Invest 2001 81 767-9. 

Trott, D.A., Newbold, R.F., and Nabholz, M. (2003). A chromosome 3-encoded repressor of the human telomerase reverse transcriptase (hTERT) gene controls the state ofhTERT chromatin. Gancer Res. 63, 689-695. 

Rufer, N., Migliaccio, M., Antonchuk, J., Humphries, R. K., Roosnek, E., and Lansdorp, P.M. (2001). Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential. Blood 98, 597-603. 

Wooten-Blanks, L.G., Song, P., Senkal, C.E., and Ogretmen, B. Mechanisms of ceramide-mediated repression of the human telomerase reverse transcriptase promoter via deacetylation of Sp3 by histone deacetylase 1. Faseb J, 21, 2007, 3386-3397. 

Wooten, L.G. and Ogretmen, B. Spl/Sp3-dependent regulation of human telomerase reverse transcriptase promoter activity by the bioactive sphingolipid ceramide. J Biol Chem, 280, 2005, 28867-28876. 

The usefulness of genetic modification of cells which are to be used in engineering tissue is evidenced by non-mahgnant transformation with human telomerase reverse transcriptase of adrenocortic bovine ceUs. ... 

Retroviral-mediated transduction of liTERT (human telomerase reverse transcriptase) in human dermal microvascular endothelial cells (EC) (HDMEC) results in cell hues that form microvasculai stractures upon subcutaneous implantation in severe combined immunodeficiency mice (SCID) mice. Anti-human type IV collagen basement membrane immu-noreactivity and visualization of enhanced green fluorescent protein (eGEP)-labeled microvessels confiimed the human origin of these vessels. Piimaiy HDMEC-derived vessel density decreased with time, while telomerized HDMEC maintained durable vessels six... 

Figure 10.11 Schematic diagram of (a) formation of small interfering RNA (siRNA) loaded polyethylene glycol (PEG)- carboxymethyl chitosan (CMCS)/CaP hybrid anionic nanoparticles (NPPEG-CMCS/CaP/siRNA). (b) NPPEG-CMCS/CaP/siRNA for systemic delivery of human telomerase reverse transcriptase (hTERT) siRNA in anticancer therapy.

The low frequency of MSCs in harvested tissue is another problem. In vivo cell therapy requires large numbers of cells, and insufficient cell numbers will not provide positive outcome (Habisch et al., 2007). For most of the cases, in vitro expansion is necessary to achieve adequate cells. Previous study proved that BMSCs express telomerase, which maintained telomere length many cell doublings but not thought to be immortal (Morrison et al., 1996). Moreover, some publications indicated that MSCs may lose their multipotentiality after six or seven passages in vitro culture (Colter et al., 2000, Sekiya et al., 2002). Increase the lifespan of MSCs by viral transduction of human telomerase reverse transcriptase may help to solve the problem. 

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