The findings could help researchers to prevent deleterious changes in cultured hESCs – a factor that may hamper their future medical use – advancing towards more reliable applications of stem-cells-based regenerative treatments.
The collaborative study, coordinated through an EU-funded project ESTOOLS and involving experts at the University of Sheffield, is published by the peer-review journal Nature Biotechnology.
Embryonic stem cells are studied for potential applications in regenerative cell replacement therapies because of their unique capacity to self-renew and turn into a variety of cell and tissue types, including neurons, blood cells, bone and muscle.
However, it is known that genetic changes take place in various hESC lines as they multiply in the laboratory, some of which resemble the DNA abnormalities typical of cancer cells. hESCs may also undergo other genetic changes undetectable by conventional methods, raising concerns over their medical use.
To address this issue, researchers used high resolution DNA analysis to plot the genetic changes in 17 hESC lines cultured over many generations, from the ESTOOLS consortium -the largest cluster of hESCs laboratories in Europe. Authors of the study include several partners of the ESTOOLS consortium, including Prof Riitta Lashema and colleagues in Turku, Finland.
The study mapped hundreds of copy number variations (CNV) and loss of heterozigosity (LOH) after prolonged passages in culture. Both CNV and LOH are genetic variations that that may be associated with tumour transformation.
For the first time, researchers could shortlist a number of genes that map inside or near the mutated sites, and that could therefore be affected by these potentially deleterious changes.
Professor Peter Andrews, from the University of Sheffield’s Department of Biomedical Sciences and a leading author of the study, said: “When we know which genes are involved, it will be easier to reject those hESC lines in which those genes are more likely to mutate.”
Authors point out that the study will also help to dig into the so-called culture adaptation process, i.e. the accumulation of genetic changes typical of malignant transformation that is mimicked by hESCs in culture, potentially providing clues to some of the genetic mechanisms underlying cancer development.
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