Scientists once believed that human embryonic stem cells were extraordinarily stable in culture. In 2004, Peter Andrews at the University of Sheffield, UK, and colleagues revealed definitive evidence that lines can develop chromosomal abnormalities.1 Sheffield's group discovered three independent human embryonic stem cell lines that gained chromosome 17q on five independent occasions, after 22 to 60 passages, and occasionally gained chromosome 12. Both are aberrations commonly seen in human embryonal carcinoma cells.
Although suspected for some time, the evidence that such chromosomal changes took place served as a rallying call in the aftermath of federal restrictions placed on human embryonic stem cell lines created after 2001. "The million dollar question that now needs to be answered is what the functional consequences of these changes are" for stem cell therapies, says Anirban Maitra at Johns Hopkins University. Research should also investigate what the mutation rates of human embryonic stem cells are, compared with other cells, and whether culture conditions exist to minimize these abnormalities, Andrews says. Future experiments should pinpoint which genes duplicated in the chromosomal gain that might confer selective advantages for the cells in culture, says Mahendra Rao at the National Institute on Aging in Baltimore. These aberrations could shed light on cancer progression, Andrews says.1. J.S. Draper et al., "Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells." Nat Biotechnol, 22:53-4, 2004. (Cited in 109 papers)