The pattern of genetic alterations in cultured human pluripotent stem cells

by Alexey Bersenev on November 29, 2011 · 0 comments

in embryonic/iPS

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A few years ago, International Stem Cell Initiative launched a big global collaborative project, which was aimed to compare genetic stability/ difference between many pluripotent (embryonic stem (ES) and iPS cell) stem cell lines across the laboratories. The results of this ambitious project were just published.

The scale of the project is enormous: 125 human ES and 11 iPS cell lines from 38 laboratories of 19 countries! I was very happy to see an example of how international scientific collaboration could work for large-scale projects. Unfortunately, results of the survey is not on a public domain.

The study demonstrates that significant part of cell lines accumulate genetic alterations in prolonged culture. One of the strong patterns that they identified was amplification of BCL2L1 gene. This gene is encoding apoptosis inhibitor. So what are the consequences of this study? I’d like to quote some excerpts from the Scientist magazine:

Such genetic changes to hESCs might appear to put the kibosh on plans for their use in patients. However, Andrews insisted that the finding was “not a disaster.” For one thing, the amplification of BCL2L1, like other changes, was more common in hESC that had been cultured for a long time, indicating that younger cultured cells may contain fewer genetic differences. Furthermore, the majority of the cell lines analyzed remained at least karyotypically normal – that is, they did not have large-scale changes.

“What it says from a safety and application point of view is that we can grow cells and we can expect them to remain genetically normal, but we have to monitor them,” Andrews said. “Because if you grow the cells for sufficient time there is a likelihood that they will acquire changes, and that these changes will be non-random.”

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