Accumulation of Abnormalities

Indianapolis, IN -

It is known that embryonic stem cells offer almost limitless possibilities for regenerative medicine. In fact, there are reports in the published literature that human embryonic stem cells have actually been used clinically.

One of the important aspects of these cells is their high level of telomerase expression which allows almost indefinite proliferation without senescence. However this may have disadvantages in terms of possibilities of cancer formation.

In a recent paper (Mantel et al. Checkpoint-Apoptosis uncoupling in human and mouse embryonic stem cells: a source of karyotypic instability. Blood. 2007 Feb 8) the acquisition of mutations in embryonic stem cells was studied using chromosomal instability as a means of detection. The investigators found that the mitotic-spindle-checkpoint, which is important in ensuring proper chromosomal integrity does not initiate apoptosis during chromosomal instability. In non-ES cells,polyploidy or aneuploidy triggers a program of cellular suicide which prevents the cells with damaged genetic material from proliferating and "continuing" the cellular errors. It appears from the paper that this mechanism is non-functioning in embryonic stem cells.

Although this does not come as a big surprise given all the similarities between ES cells and tumor cells, the main question is whether cells differentiated in vitro from ES cells are also tolerant to mutations. This should not be the case, but it would be interesting to find out.