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Stem Cell Mutations Explored

By Stephen Luntz

Why do some stem cells acquire genetic mutations when cultured?

The fact that pluripotent stem cells sometimes become genetically unstable has been one of the major barriers to the use of stem cells to treat medical conditions.

An international study has provided some hints as to why some stem cells acquire genetic mutations when cultured, with Nature Biotechnology reporting the results after culturing 127 human embryonic stem (HES) cells lines and 11 induced pluripotent (iPS) stem cell lines.

“While it is reassuring that 75% of the stem cell lines studied remained normal after prolonged growth in the laboratory, detecting and eliminating abnormal cells is an absolute prerequisite for clinical use of stem cell products,” says Prof Martin Pera of Stem Cells Australia and co-author of the paper.

The cell lines were taken from an ethnically diverse population, but if there was a pattern to the instability Pera says it may be in where and how the culturing was done. “There are a number of different culturing techniques, and it may be that some are more prone to abnormalities than others,” he says.

Some labs had abnormality rates well above the 25% average, and Pera says this may result from a preference for a particular method, although the fact that a lab will often deal with similar cell lines could also be a factor.

“Mutations are probably popping up randomly all the time, just as in cells in the body as you age,” Pera says. “If a mutation provides a selective advantage in non-optimal conditions it will expand and grow. Many of the versions are the same as those seen in cancer.”

The prospects of mutation increase the longer the culturing is repeated, but Pera notes that some lines “were cultured for very long periods and remained normal”. He adds that treatments would involve producing a bank of cells to be expanded when necessary “rather than going back to the original cell line”.

The study found a slightly higher rate of mutation in iPS lines than HES, but the sample size was far too small for statistical confirmation. Nevertheless, such a pattern would not be a surprise.

“iPS cells are taken from a patient who is older, so the cells may have already acquired mutations,” Pera says. “Some people also think the reprogramming process used for iPS cells itself may induce genetic changes.”