Lab-grown ‘mini kidneys’ for testing PKD treatments
We interview Professor Patricia Wilson, Trustee of the PKD Charity and Curator of the PKD BioResource, to find out more about new research into the use of lab-grown ‘mini kidneys’ to find new treatments for PKD.
The PKD Charity is funding a 3-year research project at University College London that will test out possible treatments for PKD on kidney organoids. Organoids are living lab-grown three-dimensional groups of cells that act like simple, mini versions of the kidneys.
A PhD student will do the research with guidance from supervisors Professor Jill Norman and Professor Patricia Wilson. To begin, the student will refine the process of making kidney organoids from the cells of people with PKD. They will then see how the organoids respond to different drugs, with an aim to find potential new treatments for PKD.
Pat tells us more…
There are many areas of PKD to research – why study organoids in particular?
Up until now, testing of potential new drug therapies has been carried out in mouse models of PKD or in single layers of human PKD cells in culture dishes. Using organoids overcomes the disadvantages of these previous approaches. They are three-dimensional structures containing many different cell types of the human kidney cells organised in the same way as in a whole kidney but accessible for direct treatment and rapid study in a culture dish.
How big is an organoid – can you see it with the naked eye?
They are very small but can vary in size from as thin as a hair to up to about 5 mm (the width of a child’s fingernail).
How is an organoid different to a whole kidney?
The organoids begin as a single cell in a dish that multiplies. The cells mature over a few days to form a complex interacting body. Most of the cells are kidney tubules and supporting cells. However, organoids do not usually contain organised blood vessels or nerves, unlike a whole kidney.
Organoids are grown from a special cell known as a stem cell. What is a stem cell?
A stem cell is a cell from which all the different types of cell can develop. The cell repeatedly divides, giving rise to daughter cells which mature and develop characteristics of, e.g., kidney cells.
How do you get stem cells from people with PKD?
PKD stem cells are extracted from PKD kidneys that have been donated for research and preserved by special protective freezing techniques.
How do you ‘tell’ a stem cell to grow into a kidney organoid?
They are “induced” to grow by adding specific combinations of signalling molecules called growth factors in a semi-solid matrix (like a jelly) to support the cells.
Do PKD organoids show similar abnormalities to PKD kidneys?
Yes, this is what makes them so useful for research.
If potential new treatments are found through this research, what is the next step?
They would be tested extensively to work out the best dose and to make sure there were no side effects, first in cultures and then in humans in Phase 1 safety trials.
Has organoid research led to interesting findings in other diseases?
Yes, in various other organs such as the liver, intestine, and brain and in cancers.
Do you think that one day it will be possible to grow a whole kidney in the lab?
Probably, although there are many layers of tissue organisation to achieve.
You also curate the PKD BioResource. What is this and how is it being used in research?
This is a resource designed to archive and store for future use a large numbers of ADPKD and ARPKD kidney tissues and cell cultures. These are then offered to all researchers in the UK for use in their approved studies. The goal is to provide a stimulus and help accelerate research into PKD by many investigators.
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