Kidneys play a crucial role by filtering waste from all of the blood in our bodies - and as frequently as several times a day. Photo / 123RF
Kidneys play a crucial role by filtering waste from all of the blood in our bodies - and as frequently as several times a day. Photo / 123RF
A renowned Kiwi scientist's research could point the way to bio-engineering new kidneys.
The bean-shaped organs play a crucial role by filtering waste from all of the blood in our bodies – and as frequently as several times a day.
But high nationwide rates of kidney disease - particularly among Māori and Pacific populations – have brought an urgent need for new therapies.
One promising avenue is using kidney stem cells to effectively grow new kidneys for affected patients, yet this can't be done until we properly understand how they normally form within an embryo.
It's here that Associate Professor Alan Davidson, the head of the University of Auckland's Department of Molecular Medicine and Pathology, has made some exciting strides.
During embryonic development, different progenitor cells migrate from particular developmental structures to other sites to form the various organs found in an adult.
In the kidney's case, the organ comes from one of three germ layers of vertebrate embryos, called the mesoderm.
Within the mesoderm itself, it originates from a subset that lies between one region that makes muscle from blocks called somites, and another called the lateral plate, which creates the lining of some blood vessels and tissue around the intestines.
From studies dating back over 150 years, scientists believed this was the only place kidney cells could come from.
Associate Professor Alan Davidson of the University of Auckland, has made some exciting strides toward bio-engineered kidneys. Photo / Supplied
But that was until Davidson discovered a new source of them, within the area that made somites.
This breakthrough was made by studying zebrafish, which share nearly three quarters of the same genes we have.
Further, Davidson has shown that these recently identified cells could form new functional tissue when transplanted into damaged kidneys.
In a new, three-year study, being supported with a $934,000 grant from the Marsden Fund, Davidson will characterise these cells and find out whether they can be exploited for new therapies.
First, that means taking somites from an embryo that has been fluorescently marked, and then transplanting them into a host embryo where they will be tracked.
"We will be looking to see if somite-derived cells end up contributing to the kidney tubules."
Secondly, the project would use the latest gene-editing technology – CRISPR/Cas 9 – to brand a series of transgenic embryos with DNA barcodes.
"Using this, we can trace the ancestry of the cells to work out whether muscle and kidney share a common cellular ancestor," Davidson said.
"This will be a challenge as we need to sequence and computationally analyse tens of thousands of cells."
But if the study proves successful, the textbook description of kidney formation would be turned on its head.
"This is fundamental science at its core – but it has applications for tissue-engineering efforts to make kidneys from stem cells."
In a separate programme, Davidson and colleagues have been turning human stem cells into kidney "organoids" – or mini-organs grown in a dish.
"Knowing that kidney progenitors could come from an alternative source of mesoderm may allow us to develop different – and better - methods to make these organoids," he said.
"Ultimately in the future we want to transplant engineered kidneys or renal progenitors into patients with kidney failure, as an alternative to donor transplants."
