DNA damage caused by factors such as ultraviolet radiation affect nearly three-quarters of all stem cell lines derived from human skin cells, say Cambridge Researchers, who argue that whole genome sequencing is essential for confirming if cell lines are usable.
Stem cells are a special type of cell that can be programmed to become almost any type of cell within the body. They are currently used for studies on the development of organs and even the early stages of the embryo.
Increasingly, researchers are turning to stem cells as ways of developing new treatments, known as cell-based therapies. Other potential applications include programming stem cells to grow into nerve cells to replace those lost to neurodegeneration in diseases such as Parkinson’s.
researchers at the University of Cambridge and Wellcome Sanger Institute have discovered a problem with stem cell lines derived from both skin cells and blood. When they examined the genomes of the stem cell lines in detail, they found that nearly three quarters carried substantial damage to their DNA that could compromise their use both in research and, crucially, in cell-based therapies. Their findings represent the largest genetic study to date of iPSCs and are published today in Nature Genetics.
DNA is made up of three billion pairs of nucleotides, molecules represented by the letters A, C, G and T. Over time, damage to our DNA, for example from ultraviolet radiation, can lead to mutations – a letter C might change to a letter T, for example. ‘Fingerprints’ left on our DNA can reveal what is responsible for this damage. As these mutations accumulate, they can have a profound effect on the function of cells and in some cases lead to tumours.
The researchers used a common technique known as whole genome sequencing to inspect the entire DNA of stem cell lines in different cohorts, including the HipSci cohort at the Wellcome Sanger Institute and discovered that as many as 72% of the lines showed signs of major UV damage.
“If a line is to be used for cell based therapies in patients for example, then we need to understand more about the implications of these mutations so that both clinicians and patients are better informed of the risks involved in the treatment.”
The research was funded by Cancer Research UK, the Medical Research Council and Wellcome, and supported by NIHR Cambridge Biomedical Research Centre and the UK Regenerative Medicine Platform.
Source: University Of Cambridge