London: Wednesday 07 October 2015 18:00 (BST)
Sydney: Thursday 08 October 2015 04:00 (AEDT)
Lab-cultured human stem cells are used to grow structures that resemble an embryonic kidney, reports a study published online in Nature this week. The work represents an important step towards building fully functional stem-cell-derived kidneys, and suggests that the kidney-like structures may prove useful for drug toxicity screening, genetic disease modelling and as a source of specific kidney cell types for treatment.
The human embryonic kidney develops from two precursor (progenitor) cell populations: one goes on to form the collecting ducts of the kidney, and the other the functional nephrons. The authors have previously shown that human pluripotent stem cells (hPSCs) — those that can develop into any kind of cell type — can be directed to form both types of progenitor populations simultaneously.
Minoru Takasato, Melissa Little and colleagues identify the signalling factors and conditions that regulate whether hPSCs become either collecting duct or nephron progenitors. They then use this knowledge to grow kidney-like structures (organoids), which contain nephrons associated with a collecting duct network, but also the connective tissue and blood vessel progenitor cells that normally surround nephrons in human embryos. The genes expressed in the kidney organoids are similar to those expressed in the kidneys of first-trimester human fetuses, and the organoids show damage when exposed to known renal toxins.
In an accompanying News & Views article, Jamie Davies comments that it is important to emphasize that the organoids are not kidneys. “The structure’s fine-scale tissue organization is realistic, but it does not adopt the macroscale organization of a whole kidney…There is a long way to go until transplantable kidneys can be engineered, but Takasoto and colleagues’ protocol is a valuable step in the right direction.”
Melissa Little
Murdoch Childrens Research Institute, Parkville, Australia
Email: melissa.little@mcri.edu.au
, Tel: +61 03 99366206
This author can also be contacted via:
Simone Myers
Murdoch Childrens Research Institute
+61 8341 6433 or +61 407 852 335
10.1038/nature15695
http://nature.com/articles/doi:10.1038/nature15695
* Please link to the article in online versions of your report (the URL will go live after the embargo ends).
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Image 1
Caption: Image of a mini-kidney formed in a dish from human induced pluripotent stem cells.
Credit: Minoru Takasato
Image 2
Caption: Kidney organoid in a dish generated from human pluripotent stem cells. The three colours show the presence of distinct cell types within the developing nephrons.
Credit: Fabian Fromling and Minoru Takasato
Video 1
Caption: Movie showing the structures present within a mini-kidney scanning from the bottom of the organoid to the top. At the bottom you can see the branching collecting ducts which are connected to the tubules of the nephrons (yellow then red) which in turn attach to the glomeruli
(green) at the top.
Credit: Minoru Takasato
URL: https://www.youtube.com/watch?v=075Vit5108w
Video 2
Caption: Movie showing the structures present within a mini-kidney scanning from the bottom of the organoid to the top. At the bottom you can see the branching collecting ducts which are connected to the tubules of the nephrons (yellow then red) which in turn attach to the glomeruli
(green) at the top.
Credit: Minoru Takasato
URL: https://www.youtube.com/watch?v=ksU6qudLy0I
Video 3
Caption: Movie scanning through a kidney organoid showing the blood vessels (pink cells) beginning to grow into the forming glomeruli (balls of green cells).
Credit: Minoru Takasato
URL: https://www.youtube.com/watch?v=Q1mPZwGIh-4