Patient's own cells may hold therapeutic promise after reprogramming, gene correction

Scientists from the Morgridge Institute for Research, the University of Wisconsin-Madison, the University of California and the WiCell Research Institute moved gene therapy one step closer to clinical reality by determining that the process of correcting a genetic defect does not substantially increase the number of potentially cancer-causing mutations in induced pluripotent stem cells.

Their work suggests that human induced pluripotent stem cells altered to correct a genetic defect may be cultured into subsequent generations of cells that remain free of the initial disease.

However, although the gene correction itself does not increase the instability or the number of observed mutations in the cells, the study reinforced other recent findings that induced pluripotent stem cells themselves carry a significant number of genetic mutations.

"This study showed that the process of gene correction is compatible with therapeutic use," says Sara Howden, primary author of the study, who serves as a postdoctoral research associate in James Thomson's lab at the Morgridge Institute for Research. "It also was the first to demonstrate that correction of a defective gene in patient-derived cells via homologous recombination is possible."

Like human embryonic stem cells, induced pluripotent stem cells can become any of the 220 mature cell types in the human body. Induced pluripotent stem cells are created when skin or other mature cells are reprogrammed to a pluripotent state through exposure to select combinations of genes or proteins.

Since they can be derived from a patient's own cells, induced pluripotent stem cells may offer some clinical advantages over human embryonic stem cells by avoiding problems with rejection. However, scientists are still working to understand subtle differences between human embryonic and induced pluripotent stem cells, including a higher rate of genetic mutations among the induced pluripotent cells and evidence that the cells may retain some "memory" of their previous lineage.