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

Feb 10, 2012

A research group including Kyoto University researchers demonstrates that mouse iPS cells, in which genetic correction occurs spontaneously through mitotic recombination, is selectable from the population of genetically mutated iPS cells in the mouse model of autosomal dominant polycystic kidney disease (ADPKD). This technology could be applicable of genome editing in human iPS cells for curing patients with genetic disorders.

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

Induced pluripotent stem cells (iPSCs) generated by epigenetic reprogramming of personal have limited therapeutic capacity for patients suffering from genetic disorders. Here we demonstrate restoration of a genomic mutation heterozygous for Pkd1 ( 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 , offering an invaluable step forward for patients carrying a wide range of genetic disorders.

Explore further: Herpes virus hijackers

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

Related Stories

Could patients' own kidney cells cure kidney disease?

Jul 27, 2011

Approximately 60 million people across the globe have chronic kidney disease, and many will need dialysis or a transplant. Breakthrough research published in the Journal of the American Society Nephrology (JASN) indicates that p ...

Adult stem cells take root in livers and repair damage

May 11, 2011

Johns Hopkins researchers have demonstrated that human liver cells derived from adult cells coaxed into an embryonic state can engraft and begin regenerating liver tissue in mice with chronic liver damage.

Recommended for you

Herpes virus hijackers

May 22, 2015

The virus responsible for the common cold sore hijacks the machinery within our cells, causing them to break down and help shield the virus from our immune system, researchers from the University of Cambridge ...

Bacteria cooperate to repair damaged siblings

May 21, 2015

A University of Wyoming faculty member led a research team that discovered a certain type of soil bacteria can use their social behavior of outer membrane exchange (OME) to repair damaged cells and improve ...

New antibody insecticide targets malaria mosquito

May 20, 2015

Malaria is a cruel and disabling disease that targets victims of all ages. Even now, it is estimated to kill one child every minute. Recent progress in halting the spread of the disease has hinged on the ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.