Human embryonic stem cells: long term stability, absence of senescence and a potential cell source for neural replacement.

Unlike normal somatic cells, human embryonic stem cells (hESCs) can proliferate indefinitely in culture in an undifferentiated state where they do not appear to undergo senescence and yet remain nontransformed. Cells maintain their pluripotency both in vivo and in vitro, exhibit high telomerase activity, and maintain telomere length after prolonged in vitro culture. Thus, hESCs may provide an unlimited cell source for replacement in a number of aging-related neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease as well as other neurological disorders including spinal cord injuries. The ability of hESCs to bypass senescence is lost as hESCs differentiate into fully differentiated somatic cells. Evidence has been accumulated that differences in telomere length, telomerase activity, cell cycle signaling, DNA repair ability, as well as the lack of genomic, mitochondrial and epigenetic changes, may contribute to the lack of senescence in hESC. In this manuscript, we will review recent advances in characterizing hESCs and monitoring changes in these aspects in prolonged cultures. We will focus on the potential roles of several cellular pathways including the telomerase, p53 and the Rb pathways in escaping senescence in hESCs. We will also discuss the genomic and epigenetic changes in long-term hESC culture and their potential roles in bypassing senescence.