Led by the Biomedicum Stem Cell Centre at the University of Helsinki in Finland and the Samuel Lunenfeld Research Institute of the Mount Sinai Hospital in Canada, the scientists showed that the reprogramming process for generating iPS cells - cells that can then be 'coaxed' to become a variety of cell types for use in regenerative medicine - is associated with inherent DNA (deoxyribonucleic acid) damage.
This damage is detected in the form of genetic rearrangements and "copy number variations" - alterations of DNA in which a region of the genome is either deleted or amplified on certain chromosomes. The variability may either be inherited, or caused by de novo mutation.
"Our analysis shows that these genetic changes are a result of the reprogramming process itself, which raises the concern that the resultant cell lines are mutant or defective," says Dr Andras Nagy, a senior investigator at the Lunenfeld Institute. "These mutations could alter the properties of the stem cells, affecting their applications in studying degenerative conditions and screening for drugs to treat diseases. In the longer term, this discovery has important implications in the use of these cells for replacement therapies in regenerative medicine."
His colleague, post-doctoral scientist Dr Samer Hussein, says the study also "highlighted the need for rigorous characterisation of generated iPS lines, especially since several groups are currently trying to enhance reprogramming efficiency".
He gave the following example to illustrate this point. "Increasing the efficiency of reprogramming may actually reduce the quality of the cells in the long run, if genomic integrity is not accurately assessed."
Stem cells have been widely touted as a source of great hope for use in regenerative medicine, as well as in the development of new drugs to prevent and treat illnesses including Parkinson's disease, spinal cord injury and macular degeneration. But techniques for generating these uniquely malleable cells have also opened a Pandora's Box of concerns and ethical quandaries. The EU, Health Canada and the US Food and Drug Administration (FDA) consider stem cells to be drugs under federal legislation, and as such, subject to the same regulations.
"Our results suggest that whole genome analysis should be included as part of the quality control of iPS cell lines to ensure that these cells are genetically normal after the reprogramming process, and then use them for disease studies and/or clinical applications," Dr Nagy says.
Says Dr Timo Otonkoski from the Biomedicum Stem Cell Centre: "Rapid development of the technologies in genome-wide analyses will make this more feasible in the future. A need to further explore if other methods might mitigate the amount of DNA damage generated during the generation of stem cells."
For more information, please visit:
- Nature, http://www.nature.com
- Biomedicum Stem Cell Centre, http://research.med.helsinki.fi/neuro/Otonkoski/
- ESTOOLS, http://www.estools.eu
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