This paper was issued to PLoS ONE at 14:00 (PST) on February 9 2012.

Induced pluripotent stem cells (iPSCs) generated by epigenetic reprogramming of personal somatic cells have limited therapeutic capacity for patients suffering from genetic disorders. Here we demonstrate restoration of a genomic mutation heterozygous for Pkd1 (polycystic kidney disease 1) deletion (Pkd1(+/-) to Pkd1(+/R+)) by spontaneous mitotic recombination.

Notably, recombination between homologous chromosomes occurred at a frequency of 1-2 per 10,000 iPSCs. Southern blot hybridization and genomic PCR analyses demonstrated that the genotype of the mutation-restored iPSCs was indistinguishable from that of the wild-type cells.

Importantly, the frequency of cyst generation in kidneys of adult chimeric mice containing Pkd1(+/R+) iPSCs was significantly lower than that of adult chimeric mice with parental Pkd1(+/-) iPSCs, and indistinguishable from that of wild-type mice.

This repair step could be directly incorporated into iPSC development programmes prior to cell transplantation, offering an invaluable step forward for patients carrying a wide range of genetic disorders.

More information: Cure of ADPKD by selection for spontaneous genetic repair events in Pkd1-mutated iPS cells, Li-Tao Cheng, et al. Stem Cell Engineering, Institute for Frontier Medical Scinences, Kyoto University, JAPAN, Urology, Teikyo University, JAPAN, Cardiovascular and Neuronal Remodelling, LIGHT, Leeds University, UK, PLoS ONE 7(2): e32018. doi:10.1371/journal.pone.0032018

Provided by Kyoto University

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Cure of ADPKD by selection for spontaneous genetic repair events in Pkd1-mutated iPS cells