Stem cells undergo evolution in the lab

Stem cells evolve, even in the lab. This is the finding made by researchers in the International Stem Cell Initiative, and it has implications on how stem cells are used for therapeutic applications.

The study is the largest to date on the genetic stability of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), and was conducted on cell lines from 38 laboratories worldwide.

It’s been known that some hESCs mutate in the lab, and often in non-random ways, with the researchers in this study finding a progressive tendency to acquire changes particularly in chromosomes 1, 12, 17 and 20.

While around two thirds of the cultures examined remained karyotypically normal, even after many generations, another third exhibited genetic changes.

It appears that some of these mutations often select for greater self-renewal, effectively ‘adapting’ to the environment of the culture, which is an example of evolution at work in the lab.

The researchers consider this increase in frequency of genetic variants in embryonic stem cell cultures could be be inevitable.

While many mutations found were random, over 20 per cent of the cell lines examined showed signs of amplification in a specific region of chromosome 20.

This region contains three genes, and one of them, BCL2L1, proved to be a strong candidate for driving hESC culture adaptation.

The study also found “haphazard” changes in DNA methylation patterns in the stem cells which appeared to have no link to the culture, suggesting epigenetic changes are common.

It is hoped that this understanding of how cultured embryonic stem cells can change in the lab can be used to better evaluate the cells for potential therapeutic applications and screen out inappropriate cells.

The study, which involved researchers from the University of Melbourne, Monash University, the University of New South Wales and the CSIRO, was published in Nature Biotechnology today.