Epidermolysis bullosa simplex keratinocytes with extended lifespan established by ectopic expression of telomerase.
As part of a strategy to develop somatic gene therapy of epidermolysis bullosa simplex (EBS) we have established patient keratinocytes with expanded lifespan by ectopic expression of the human telomerase gene (hTert). The presence of an active telomerase enzyme was demonstrated by the telomerase repeat amplification protocol (TRAP). The hTert(+) cells have a normal karyotype and the cells have, until now, undergone more than 80 population doublings (PDs) after hTert retroviral transduction while control cells exhibited senescence-associated proliferation arrest after 8 PDs. In organotypic culture the hTert(+) cells are capable of forming a stratified epidermis illustrating their preserved ability to differentiate.
Jensen
Thomas G
TG
Department of Human Genetics, University of Aarhus, 8000 Aarhus C, Denmark. thomas@humgen.au.dk
Sørensen
Charlotte B
CB
Jensen
Uffe B
UB
Bolund
Lars
L
D002461:Cell Line, Transformed; D002470:Cell Survival; D003584:Cytological Techniques; D016110:Epidermolysis Bullosa Simplex / Q000473:pathology*; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000502:physiology*; D007633:Keratins / Q000502:physiology; D019098:Telomerase / Q000378:metabolism*
D007633:Keratins; D019098:Telomerase