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J Biol Chem, Vol. 274, Issue 37, 26141-26148, September 10, 1999
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From the Departments of Normal human endothelial cells, like other
somatic cells in culture, divide a limited number of times before
entering a nondividing state called replicative senescence. Expression
of the catalytic component of human telomerase, human telomerase
reverse transcriptase (hTERT), extends the life span of human
fibroblasts and retinal pigment epithelial cells beyond senescence
without causing neoplastic transformation (Bodnar, A. G.,
Ouellette, M., Frolkis, 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) Nat.
Genet. 21, 111-114). Here, we show that both human large vessel
and microvascular endothelial cells also bypass replicative senescence
after introduction of hTERT. For the first time, we report that hTERT
expression in these life-extended vascular cells does not affect their
differentiated and functional phenotype and that these cells maintain
their angiogenic potential in vitro. Furthermore, hTERT(+)
microvascular endothelial cells have normal karyotype, and hTERT(+)
endothelial cell strains do not exhibit a transformed phenotype.
Relative to parental cells at senescence, hTERT-expressing endothelial
cells exhibit resistance to induction of apoptosis by a variety of
different conditions. Such characteristics are highly desirable for
designing vascular transplantation and gene therapy delivery systems
in vivo.
Dermatology and
¶ Cytogenetics, Stanford University School of Medicine, Stanford,
California 94305-5486 and Geron Corp., Menlo
Park, California 94025-1130
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