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DNA discovery may boost stem cell safety

Regenerative medicine A region of DNA that can boost the growth of stem cells has been found in the largest ever study of human embryonic stem cells.

The discovery could lead to safer cell therapies, says study co-author Dr Andrew Laslett from CSIRO Materials Science and Engineering.

The research by the International Stem Cell Initiative involved 38 laboratories across the globe studying 125 ethnically diverse cell lines in parallel experiments.

Study findings, reported in today's issue of Nature Biotechnology , uncover changes that arise from how cells are grown.

Embryonic stem cells are powerful for their ability to become any other cell in the body.

Stem cell therapy, which is entering early-stage human trials, turns stem cells into other cell types, like healthy nerve cells, to treat spinal cord injury, blindness and other ailments.

The cells need to be grown in nutritious culture to produce enough cells for therapy. Many stem cells die when they are first moved to a new culture, leading to natural selection and adaptation.

Cells with a growth advantage expand faster and dominate. However, this can come at the price of genetic mutation, so growing fast is not always desirable.

"It's the small fraction of cells that become abnormal that can be dangerous in a clinical situation," says Laslett. "If they find growth situations that suit them, they could grow into cancers."

One in five cell-lines mutated a particular region of chromosome 20. Gaining extra copies of the region seemed to give them a growth advantage.

From the three genes in the region, it's likely the advantage is from BCL2L1. It's known to stop controlled cell death, or apoptosis. The same mutation is also found in some cancer cells.

By targeting this region of chromosome 20, Laslett says we can "develop better tests to tell more quickly if the cells are going bad in culture."

Scientists could use these tests to improve current techniques used to grow stem cells.

"Embryonic stem cells walk a tightrope with maintaining their normal genetic nature," he says. "We need to culture them in the best possible way so they keep those genes normal."

International collaboration

Associate Professor Paul Thomas at the University of Adelaide, who was not involved in the study, says the research is impressive in its scale.

"This kind of paper wouldn't be possible without international collaboration."

"One of the interesting findings is that most of the embryonic stem cells are normal, even though they have been cultured for a long period. About two thirds were unchanged," he says.