A study in the October issue of Nature Genetics reports that human embryonic stem cell lines cultured for a long period of time develop changes in their genomes that may make them unusable for therapeutic purposes.
While all cultured cells develop small mutations over time, some previous work had suggested that large-scale genetic alterations in embryonic stem cells were rare. Using a more sensitive technique, Aravinda Chakravarti and colleagues now show that stem cell lines that are cultured at length tend to accumulate more significant changes in certain regions of the genome, including large deletions and amplifications. Some of these regions are known to be involved in human cancers.
The authors also found mutations in the mitochondrial DNA, which could affect the metabolic functions of the cells, as well as changes in the patterns of DNA methylation--a chemical mark that typically regulates the expression of genes--in most of the extensively cultured cell lines. This latter finding stands in contrast to a recent study reporting stable methylation patterns at select genes.
The authors note that embryonic stem cell lines cultured for only a short time do not exhibit these structural changes in their genomes, making them suitable for therapeutic applications. For those cell lines that have been cultured for longer periods, such as those currently approved for research funding by the US government, the authors recommend monitoring them for various types of mutations using standardized and sensitive techniques. Additional embryonic stem cell lines that have not been extensively cultured will likely be needed, they conclude.
Aravinda Chakravarti (Johns Hopkins University School of Medicine, Baltimore, MD, USA)
For abstract, click here.
(C) Nature Genetics press release.
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