Genomic Instability in Pluripotent Stem Cells: Implications for Clinical Applications

Genomic Instability in Pluripotent Stem Cells: Implications for Clinical Applications. Suzanne E. Peterson and Jeanne F. Loring; The Journal of Biological Chemistry, 289, 4578-4584. 10.1074/jbc.R113.516419 February 21, 2014

FULL TEXT PDF


There are several examples of dramatic genomic changes that appear when cells are reprogrammed. Studies of some trinucleotide repeat diseases have reported changes in the repeat length following reprogramming. Specifically, in Friedreich ataxia, the GAA/TTC triplet repeat length in the FXN (frataxin) gene appeared to change following reprogramming of patient fibroblasts

Although the probability of an FDA-approved hPSC-derived cell therapy causing harm to a patient appears to be low, the consequences of adverse events are enormous. There is an important lesson from the failures in early gene therapy trials. If even one patient is harmed in an FDA-approved trial using hPSC derivatives, all further trials will be in serious jeopardy, and the promise of stem cell therapy will be put on indefinite hold.