Researchers find that creation of induced pluripotent stem cells is linked to genetic abnormalities
Helsinki/Toronto – Induced pluripotent stem cells from a patient’s own cells must be screened for genetic failures before any clinical use, new research from Finnish and Canadian researchers suggest. In Nature the researchers from Mount Sinai Hospital and Biomedicum Stem Cell Center at University of Helsinki under Timo Otonkoski report that the reprogramming process for generating iPS cells (i.e., cells that can then be 'coaxed' into becoming a variety of cell types for use in regenerative medicine) is associated with inherent DNA damage. Carrying out genome-wide comparative SNP analyses of human iPS cells with their respective parental cells, they identified genetic rearrangements and copy number variations in each of the assessed cell lines. "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," said Dr. Nagy, a Senior Investigator at Mount Sinai Hospital. "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. "Our study highlights the need for rigorous characterization of generated iPS lines, especially since several groups are currently trying to enhance reprogramming efficiency," said Dr. Samer Hussein at Biomedicinium Stem Cell Center. "For example, increasing the efficiency of reprogramming may actually reduce the quality of the cells in the long run, if genomic integrity is not accurately assessed." Both teams found that iPS cells had more genetic abnormalities than their originating cells and embryonic stem cells. Interestingly, however, the simple process of growing the freshly generated iPS cells for a few weeks selected against the highly mutant cell lines, and thus most of the genetic abnormalities were eventually 'weeded out.'