Stem Cells Mutate in the Lab

Stem Cells Mutate Over Time

An article published in the September 4 online issue of Nature Genetics reporting that stem cells mutate under laboratory conditions has received a lot of press.

An article on Newswise reports on a study appearing in the September 4 online edition of Nature Genetics. In the study, researchers from Johns Hopkins Medical Center in the United States and 3 other countries compared "early" and "late" stem cells from 9 of the 22 lines eligible for US federal funding. They found that genetic changes had occurred in the cells as they grew in the laboratory. The researchers examined the "epigenetic marks," methyl groups related to protein production, and found changes in mitochondrial DNA in 2 lines and extra or fewer copies of genetic material in 5 lines. All 9 lines had shifts in the methylation on at least 1 of 3 genes.

Genetic Engineering News gave a detailed report of the same issue. According to this article, the researchers used two GeneChip microarrays to analyze the stem cells' genes as a whole and to specifically examine the mitochondrial genome. They analyzed the exact order of every base (C,T,G, and A molecules) in each stem cell’s mitochondria. This report was based on a press release from Affymetrix, the manufacturer of the microarrays. According to this article, the researchers were able to use the new technology to scan the genetic material in much more detail than could previously be done with a microscope, and to much more quickly sequence the mitochondrial DNA.

This study was also reported on Lifesite.net on September 6. According to that article, "Chakravarti’s research team found that as they were cultured, stem cell lines went through 35 cell divisions and found that 90% showed changes in patterns of methylation – the process in which certain genes in a cell are turned on or off – 22% had mutations in mitochondrial DNA and 50% had major deletions or amplifications in the DNA. Moreover, it was the connection between the particular genetic problems the cells developed and the formation of tumours that was most worrying. "

Reason On-Line gives an account of the basic material researchers used. Some stem cells are frozen after dividing only a few times, while others divide many more times, and researchers compared the early and late ones with each other. Most of the changes found amplify the effect of genes that cause cancer or disable tumor-suppressant genes. One of the consequences of this study is that the stem cells used by federally funded researchers are now more limited, as cells from later lines are likely to have mutated. The article quotes one of the researchers, Dan Arking, as pointing out that cells grown from adult stem cells are even more likely to mutate.

Wisconsin Technology Network gave its version of the same study on September 7, 2005. In this article written for the layperson, researchers from the University of Wisconsin weighed in on the issue, with Dr. Stephen Duncan stating that the mutations had a negative side for stem cell research. On the other hand, Dr. Gabriela Cezar said that the “raw” stem cells themselves are not used in treatment, and it is important to look at the new cells generated by the stem cells. The article concludes with the issue of how this limits the use of the federally funded stem cell lines in both research and treatment.