Genetic changes in cultured ES cells

The largest study to date on the genetic stability of cultured human embryonic stem cells (hESCs) is published this week in Nature Biotechnology. The analysis of 125 ethnically diverse hESC lines originating from 38 laboratories around the world sheds light on the question of whether genetic mutations in the cells are related to the nature of the cells themselves or to the techniques used to grow them in culture. HESCs show promise for cell therapy because in principle they can be converted into any cell type in the body and because they are able to grow and divide indefinitely in the laboratory. But during long-term culture, the cells can acquire genetic mutations, and some of these mutations could compromise the cells’ utility for regenerative medicine. It is believed that mutations that arise and endure over long-term culture provide a selective advantage for the cells, such as a greater propensity for self renewal. Peter W Andrews and colleagues at the International Stem Cell Initiative carried out genetic analysis of a broad range of hESC lines at early and late stages of culture. Although most of the mutations they identified seemed to occur randomly, about 20% of the cell lines acquired amplifications of a specific region in chromosome 20. This region contains three genes, and one of them, BCL2L1, proved to be a strong candidate for driving hESC culture adaptation. The data generated in this study will be useful for understanding the frequency and types of genetic changes affecting cultured hESCs, an important issue in evaluating the cells for potential therapeutic applications.