Instability concerns over 'old' embryo stem cells

Human embryonic stem cells (ES cells) grown for a long time in the laboratory become genetically unstable, according to a new study by an international group of researchers. The scientists, who published their findings in the journal Nature Genetics, say that many of the older cell lines they studied had acquired genetic changes linked to human cancers. The researchers say that the results, if confirmed, show that older ES cell lines will not be suitable for therapeutic use.

All cells, whether growing in the body or the laboratory, are increasingly prone to genetic changes each time they divide and multiply to make new 'daughter' cells. But previous research showed that ES cells - the body's 'master cells' capable of growing into any type of tissue - were far more genetically stable compared to other types of cells grown in the laboratory.

President Bush's policy on human ES cell research permits federally funded scientists to carry out research on cell lines created before 9 August 2001, but researchers have complained that this policy leaves only less effective cell lines for them to work on. In the latest research, scientists from Johns Hopkins University in Baltimore and colleagues in Sweden, Canada, Singapore and the US studied nine of these approved cell lines.

The team compared cells currently growing in the laboratory with frozen samples from the same cell lines. The latest cells had typically undergone 22-175 more 'passages' than the earlier cells. The passage number refers to the number of times that a sample of cells has been removed from a growing cell line to start a new culture.

The team found that compared to the early samples, the later versions of four of these ES cell lines had lost some sections of DNA from their genome, and had gained extra copies of other sections. The scientists also discovered genetic changes linked to cancer in eight of the nine cell-lines. 'Some of the early embryonic stem cell passages were relatively aberration-free, at least using the technology we have access to, even at passage 30 or so, which would be unusual for most adult stem cells', said co-author Anirban Maitra.

Commenting on the study, James Battey, chair of the US National Institutes of Health stem cell task force, pointed out that the very act of repeatedly culturing cells introduces a selection process. As such, any cells that acquire genetic changes that enable them to multiply more effectively will 'ultimately take over', he told the Scientist magazine. 'These new findings are very fine scientific work, and show we need to be vigilant with these cells, especially when passaged for long periods of time', he added.

The findings are at odds with another study, published earlier this year, which suggested that human ES cells do not show signs of genetic instability when grown for extended periods in the laboratory. The research, carried out at the University of Cambridge, UK, showed that the process of 'genetic imprinting' - the 'tagging' of certain genes, which marks them as either maternal or paternal in origin - does not appear to be disrupted in ES cells grown in culture.

Aravinda Chakravarti, co-author of the latest study, stressed that findings need to be confirmed by further experiments. But if ES cells really do become unstable over time, 'then that would put limits on the practical life spans of the cells and their usefulness or therapeutic purposes', he said.