Stem Cell Therapy is Safe: Reprogramming Does Not Increase the Rate of Mutagenesis

The delay in answering this question has slowed adoption of iPSCs in biomedical research and medicine, as concerns that these cells are prone to increased numbers of genetic mutations persist.

Investigators at the [U.S.] National Human Genome Research Institute adopted a unique approach to answering the question of the possible increase in mutation rate in iSPCs by deriving fibroblast subclones and clonal iPSC lines from the same fibroblast population. This provided the investigators with parallel cell lines from the same source, only one of which having undergone the process to turn them into iPSCs.

The investigators applied next-generation sequencing to compare genomic variations in these lines. They reported in the February 6, 2017, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences that targeted deep sequencing of parental fibroblasts revealed that most variants detected in clonal iPSCs and fibroblast subclones were rare variants inherited from the parental fibroblasts. More than 90% of these mutations were random, preexisting sequence variants in small subsets of the parental fibroblast population. This data strongly suggested that reprogramming process was not mutagenic.

"This technology will eventually change how doctors treat diseases. These findings suggest that the question of safety should not impede research using iPSC," said senior author Dr. Paul Liu, senior investigator in the Translational and Functional Genomics Branch of the [U.S.] National Human Genome Research Institute.