Telomerization of Mammalian Cells and Transplantation of Telomerized Cells in Immunodeficient Mice

Telomerization is an operational term for appparent immortalization sustained by prevention of telomere shortening. It is always necessary to use the term apparent because immortalization, if taken literally, requires one to demonstrate that cells divide forever, a property that is obviously impossible to verify. In practice, for human cells, division for over 200 times is generally accepted as indicating that cells are immortalized. It has been known since the pioneering experiments of Leonard Hayflick in the 1960s that the limited replicative capacity of human cells in culture is very unlikely to be an experimental artifact but is a reproducible biological phenomenon (1 ). However, not until the discovery that the limitation in replicative capacity directly correlates with telomere shortening was the notion that it might be a culture artifact finally laid to rest (2 ,3 ). Telomeres shorten in most dividing human somatic cells because of the lack of telomerase activity that is required for telomere maintenance (4 ,5 ). The lack of telomerase activity results from the absence of expression of the reverse transcriptase subunit (TERT) of the telomerase ribonucleoprotein complex (6 ,7 ). When cells divide in the absence of telomerase activity, about 40–100 bp of the terminal telomeric repeat DNA is not replicated (4 ,5 ). This amount is a constant for various types of human cells, thus providing a kind of mitotic counter (4 ,5 ). Telomere shortening caused by lack of telomerase activity also occurs in many cell types in human tissues in an age-related fashion (8 ).