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: First detailed microscopy evidence of bacteria at the lower size limit of life

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

Malaria transmission linked to mosquitoes' sexual biology

Feb 26, 2015

Sexual biology may be the key to uncovering why Anopheles mosquitoes are unique in their ability to transmit malaria to humans, according to researchers at Harvard T. H. Chan School of Public Health and University of Per ...

Intermediary neuron acts as synaptic cloaking device

Feb 26, 2015

Neuroscientists believe that the connectome, a map of each and every connection between the millions of neurons in the brain, will provide a blueprint that will allow them to link brain anatomy to brain function. ...

Skeleton of cells controls cell multiplication

Feb 26, 2015

A research team from Instituto Gulbenkian de Ciencia (IGC; Portugal), led by Florence Janody, in collaboration with Nicolas Tapon from London Research Institute (LRI; UK), discovered that the cell's skeleton ...

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.