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Adult cells that have been reprogrammed into stem cells harbor a number of genetic mutations, some of which appear in genes that have been linked to cancer. While scientists don’t yet know how this might affect the use of the cells in medicine, they say the findings show that the cells need to be studied much more extensively.

“As we think about using [these] cells for therapy, we will want to consider what kinds of screening tests we want to do,” says Lawrence Goldstein, a professor of molecular biology at the University of California, San Diego. One of the major concerns about stem-cell-based therapies has been whether they carry a risk of cancer; both stem cells and cancer cells are distinguished by their ability to continually divide.

In two studies published today in Nature, researchers analyzed the genome of induced pluripotent stem (iPS) cells, adult cells that have been genetically or chemically reverted to the stem cell state. These cells have attracted intense interest from both scientists and the public as a potential alternative to embryonic stem cells. Like their embryo-derived cousins, iPS cells can develop into any type of tissue, making them a good candidate for cell-replacement therapies. They are also genetically matched to the patient, meaning they don’t carry the risk of immune rejection associated with existing cell transplants.

In one study, Goldstein, Kun Zhang, and collaborators at the University of California, San Diego, sequenced the gene-coding portion of the genome in 22 iPS cell lines that had been reprogrammed using several different methods. “Every cell line we looked at, we found single [genetic-letter] mutations in the protein-coding region, an average of six mutations per cell line,” says Zhang.

Different cell lines had mutations in different genes, but a disproportionate number of the mutations appeared in genes involved in cell growth or in genes that have been previously linked to cancer.

Some of the mutations probably arise from the evolutionary pressure of growing in a dish. If a random mutation that occurs during cell division helps daughter cells grow faster than others, that mutation will take root in the population. However, Zhang’s team found that the mutation rate in iPS cells is 10 times the typical rate for cultured cells.

It’s not yet clear why iPS cells have such a high mutation rate. Researchers found that roughly half the mutations occurred before reprogramming and could be found in a few cells in the initial population from which the iPS cells were derived. The others might have occurred during the process of reprogramming or as the newly created iPS cells grew. The team is now planning similar tests of embryonic stem cells.

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Credit: James Thomson, University of Wisconsin-Madison

Tagged: Biomedicine, stem cells, genome, sequencing, iPS cells, embryonic stem cells, reprogramming, mutations

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