Human endothelial cell life extension by telomerase expression

Normal human endothelial cells, like other somatic cells in culture, divide a limited number of times before entering a nondividing state called repli cative senescence. Expression of the catalytic component of human telomeras e, human telomerase reverse transcriptase (hTERT), extends the life span of human fibroblasts and retinal pigment epithelial cells beyond senescence w ithout causing neoplastic transformation (Bodnar, A. G;., Ouellette, M., Fr olkis, M., Holt, S. E., Chiu, C. P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., and Wright, W. E. (1998) Science 279, 349-352; Jiang, X, Jimenez, G., Chang, E., Frolkis, M., Kusler, B., Sage, M., Beeche, M., Bodnar, A, Wahl, G., Tlsty, T., and Chiu, C.-P. (1999) Not. Genet. 21, 111- 114). Here, we show that both human large vessel and microvascular endothel ial cells also bypass replicative senescence after introduction of hTERT. F or the first time, we report that hTERT expression in these life-extended v ascular cells does not affect their differentiated and functional phenotype and that these cells maintain their angiogenic potential in vitro. Further more, hTERT(+) microvascular endothelial cells have normal karyotype, and h TERT(+) endothelial cell strains do not exhibit a transformed phenotype. Re lative to parental cells at senescence, hTERT-expressing endothelial cells exhibit resistance to induction of apoptosis by a variety of different cond itions. Such characteristics are highly desirable for designing vascular tr ansplantation and gene therapy delivery systems in vivo.