“The kidney structures had matured to form a fully-functional unit”
Biologists have grown ‘mini-kidneys’ that can produce urine, which is a big step toward repairing damaged organs. Prof Sue Kimber of Manchester University explains
What does the kidney do?
In normal metabolism, waste products are deposited in the blood and need to be removed, so the kidney’s job is to get rid of the things we don’t want. But at the same time we have all sorts of valuable nutrients, salts and glucose and so on, and don’t want to get rid of those in the urine, so the kidney has to make sure it reabsorbs those nutrients if they’re filtered out. Parts of the kidneys do different things in this filtering and reabsorbing job, so we had to make the different parts.
How did you grow ‘mini-kidneys’?
We started out with human pluripotent stem cells [cells that can become any type of cell] and made them become specialised cells of the kidney. In this protocol, you get these different cell types being produced and then they interact with each other and almost start to develop autonomously into immature kidney structures in the Petri dish. We can make them form into little 3D structures on a suspended membrane. We took those developing cells and put them just under the skin of a mouse. We left them there for three months and were very pleased to find that the kidney structures had matured substantially. You could see cells of the blood system and the working filtration element of the kidney– the glomerulus – was maturing to form a fully functional unit.
How do you know they work?
We injected a fluorescent dye into the blood system, then looked an hour later and found that this fluorescent molecule had been filtered from the blood and ended up inside the tubules connected to the filtering unit. What that meant was that it had gone from the blood, been filtered by the glomerulus, and ended up in the tubules. These tubule cells have a re-uptake function, so that suggests they also have some functionality. In our developing kidneys, we have these different elements that should lead into a ureter, the final tube that takes the urine to the bladder. In our structures, we do not – as far as we can see – develop a ureter. So, if we were going to make a fully functional kidney, we would need a way out for the urine. When will the clinical trials start? I think probably a decade.
Why grow kidney cells?
We could use them to repair damaged kidneys.
The difficulty is, if you just inject them into the kidney, they’re not necessarily going to go to the right place. Can they survive? We don’t know. They may not be able to continue to develop and take over the function of the damaged kidney. There are a number of genetic diseases where the kidneys don’t develop correctly, and we’re also using this technology to identify pathways that don’t occur properly, so we can identify potential drug targets. Globally, about 2.6 million people need dialysis or kidney transplantation for end-stage kidney disease each year, and probably about 2.2 million people die because they can’t get treatment. But kidney transplants only extend life to a limited extent. There’s a shortage of donor kidneys, so this is a major unmet clinical need requiring an alternative solution.