IPSCs May Be Safer Than We Thought
Over a decade ago, Japanese researcher Shinya Yamanaka, M.D., Ph.D., and his graduate student Kazutoshi Takahashi, Ph.D., became the first people to demonstrate a technique to revert adult cells to the earliest stage of their development: pluripotent stem cells which can become develop into any type of body cell. Because of the nature of the technique, they called them induced pluripotent stem cells (iPSCs). The versatility of these cells was astronomical and the potential medical applications ranged from repairing eye tissue to restore vision after age-related macular degeneration, all the way to restoration of heart tissues after cardiac events.
Interest in iPSCs grew very quickly, but their adoption within the medical community has been hindered by concerns over their safety. As with all new medical innovations, wide scale use of iPSCs hasn’t been seen due to their potential risks, the primary concern being that these cells are prone to a higher rate of genetic mutations than average body cells.
A new study published in Proceedings of the National Academy of Sciences by researchers at the National Human Genome Research Institute (NHGRI) indicates that iPSCs display the same mutation rate as regular cells that have been duplicated by subcloning. Subcloning is a technique that is almost identical to the production of iPSCs, whereby single cells are cultured individually then grown into a full cell line; the only difference from iPSC production is that reprogramming factors are not present. It was the reprogramming factors present when forming iPSCs that were thought to induce increased mutations.
“This technology will eventually change how doctors treat diseases. These findings suggest that the question of safety shouldn’t impede research using iPSC,” said Dr. Paul Liu, co-author of the paper and senior investigator in NHGRI’s Translational and Functional Genomics Branch.
The team used two different sets of cells to gather their results, one set from a healthy donor and another from a donor with familial platelet disorder, a blood disease. Using skin cells from both participants, the team used both the iPSC and the subcloning techniques to establish cell lines before using DNA sequencing to compare the genomes of each cell line with the parent samples. They were able to determine that the rate of genetic mutation was the same in cells that had undergone subcloning as iPSC, indicating that the reprogramming factors did not negatively impact the integrity of the genome. Most of the variants present in both cell lines had originated in the parent cells.
The research is still new and not entirely conclusive, but it is a big step forwards in establishing the safety of what could be a very effective medical tool. “Based on this data, we plan to start using iPSCs to gain a deeper understanding of how diseases start and progress,” said Dr. Erika M. Kwon, co-author of the study and NHGRI post-doctoral research fellow. “We eventually hope to develop new therapies to treat patients with leukaemia using their own iPSCs. We encourage other researchers to embrace the use of iPSCs.”