Disease gene corrected in mini-kidney

30 April 2018
Patient derived stem cells grown into mini-kidneys, to correct the mutated gene in the dish.
Patient derived stem cells grown into mini-kidneys, to correct the mutated gene in the dish.
Patient derived stem cells grown into mini-kidneys, to correct the mutated gene in the dish.
New research led by the Murdoch Children’s Research Institute (MCRI), has combined gene editing technology with stem cell kidney regeneration to correct a patient’s gene mutation in a dish. 
This is the first time a patient has had kidney regenerated from their stem cells in Australia.
The research, led by PhD student Dr Tom Forbes and senior researcher Dr Sara Howden, is part of a regenerative medicine project in which human stem cells are used to develop mini-kidneys with a view to discovering new genes and treatments for inherited kidney disease.
In this new study, published in The American Journal of Human Genetics and involving hospitals and laboratories in Brisbane, Sydney and Melbourne, stem cells derived from a child with genetic kidney disease were grown into two sets of living mini-kidney organoids – one with her kidney disease and one in which her gene mutation was corrected.
The stem cells were created from a skin biopsy taken from 12-year-old Alexandria, who suffers from Mainzer-Saldino Syndrome, a rare genetic condition causing progressive retinal degeneration and end-stage kidney disease.
“Within the patient’s mini-kidneys, we discovered abnormally shaped cellular antennae. This showed that Alexandria’s disease exists within the mini-kidney and proves that we can use these regenerated tissues to learn about her disease,” said MCRI researcher and paediatric nephrologist, Dr Tom Forbes.

“We then used gene editing technology to correct the genetic mutation in Alexandria’s stem cells. These ‘gene-corrected’ stem cells were then grown into another set of mini-kidneys which showed the antennae were now a normal shape. So the gene-correction stopped the development of the disease within the mini-kidney.”

“By comparing the two mini-kidneys, we now have a better understanding of how this disease develops.”

Alexandria’s is the first reported case in which the effect of a gene mutation in kidney disease has been investigated using gene editing of patient stem cells to correct the genetic mutation.

“The fact that we can make kidney tissue from human stem cells and then correct any genetic mutations to study the way the disease develops is a very promising step towards developing personalised future treatment,” said MCRI senior research officer Dr Sara Howden.

At least 50% of children who require dialysis or a kidney transplant have a genetic cause for their kidney disease. For almost all of these conditions, very little is known about how the disease develops and no specific treatment exists.

“By growing mini-kidneys from a patient’s stem cells we’re hoping to find new genes responsible for kidney disease. We also hope we can test them for possible new treatments for that patient’s specific disease.”

While this latest research won’t impact Alexandria’s current condition, it does pave the way for possible treatments in future for other patients with similar renal diseases.

“There is a long way to go to make personalised treatments, but knowing we can study inherited kidney disease using a patient’s stem cells is a breakthrough step,” said Dr Howden.

Dr Tom Forbes, PhD student and Dr Sara Howden, Early Career Research are in Stem Cells Australia’s Professor Melissa Little‘s lab.

Credit: Murdoch Children’s Research Institute.

For more information:
Read the journal article.

Media Coverage:
Herald Sun “Mini-organs from stem cells used to uncover kidney disease”  – 30 April 2018.

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The Australasian Society for Stem Cell Research (ASSCR)