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: Fighting bacteria—with viruses

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

add to favorites email to friend print save as pdf

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

Fighting bacteria—with viruses

Jul 24, 2014

Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its re ...

Atomic structure of key muscle component revealed

Jul 24, 2014

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Brand new technology detects probiotic organisms in food

Jul 23, 2014

In the food industr, ity is very important to ensure the quality and safety of products consumed by the population to improve their properties and reduce foodborne illness. Therefore, a team of Mexican researchers ...

Protein evolution follows a modular principle

Jul 23, 2014

Proteins impart shape and stability to cells, drive metabolic processes and transmit signals. To perform these manifold tasks, they fold into complex three-dimensional shapes. Scientists at the Max Planck ...

Report on viruses looks beyond disease

Jul 22, 2014

In contrast to their negative reputation as disease causing agents, some viruses can perform crucial biological and evolutionary functions that help to shape the world we live in today, according to a new report by the American ...

User comments : 0