Professor Melissa Little, University of Queensland
For the first time, scientists from Australia have used stem cells to grow a new kidney in a dish. By controlling the conditions very carefully, and adding a sequence of growth factors to fool the cells into thinking they were back inside a developing embryo, they turned into kidney tissue. Melissa Little and her colleagues have manage to create the closest equivalent yet to a real kidney, as she explained to Chris Smith...
Melissa - You can take a stem cell, and we can make that from any cell in anybody’s body and actually convince that cell to go through the whole process, as it would have in development, to make a little kidney in a dish. The key is that many people have kidney disease and we really want to find a way of regenerating kidney tissue. And so, we asked if stem cells could do this.
Chris - Why is it so difficult to persuade a stem cell to turn into an organ like a kidney?
Melissa - You have really got to convince it to make the specific stem cells that form that organ. The final kidney in an adult has more than 20 to 25 different types of cells and they all have to be formed in the right place in the right time. So, what we have to do is convince the cell that it’s going through the normal processes it would go through during development. We have got to give it the right chemical signals. We have got to encourage the cells that are in there to talk to each other. It is sort of like a recipe – you have got to add the right factors at the right time, and give it the right amount of time and then amazingly, the cells that form, organise around each other to create the structure that we are looking for.
Chris - What did you start with and what did you end up with?
Melissa - We started with a stem cell that was made from a skin fibroblast. That is a cell that you can get from your skin, and then we added different factors in the dish. It takes about 3 weeks. The stem cell will start to make choices. It turns into one cell type that becomes another cell type and all of these are things that would normally happen in development. Then the cells talk to each other, and form the structure that we see eventually. So, it ends up being about a half a centimetre to a centimetre across, with about 100 little tubes in it, with blood vessels forming in a very complex little organ.
Chris - What's to stop you then growing instead of something of that scale a full size kidney and then just plumbing it into an individual?
Melissa - Technically, you should be able to make large, large numbers of these cells, but you can't keep structures that big alive without a blood supply, and we are doing this in a dish. So ultimately, it is going to be engineered so that we can provide it with a blood flow, and at the moment it doesn’t have one exit for the urine which, of course, you have got to have because the urine has got to get out of your body somehow.
Chris - Can you surmount these problems of getting the blood supply and so on because at the moment, this is in a Petri dish? How would one scale this to become a bigger kidney?
Melissa - So, can I just say, it does have blood vessels. It just doesn’t have blood flowing through it bur it has got to have a source of blood from somewhere. So yes, there are a couple of ideas, maybe if we just made large numbers of these cells and then put them back into a scaffold made from a kidney that has had all of its cells taken out, or actually bio print a structure of some sort. I guess we have in our heads this idea that you have got to build something as big as what you're replacing but dialysis, which is what a lot of kidney disease patients live on, only gives you 10 per cent kidney function. So, there is a lot of room for improvement over that.
Chris - How do you know that what you’ve created will actually work? How do you know this is functional tissue?
Melissa - We have tested some functions. Obviously, they don’t make urine because you can't make urine unless you’ve got a force of blood flowing through your structure, and this is in a dish. But we have asked things like, are the cells in that organ starting to do some of the other functions that they normally do? For example, we’ve asked, there are some drugs that are actually really toxic to the kidney. So, we’ve put on those drugs and said, “Am I seeing this specific toxicity to that drug and are these kidneys are responding the way they would in an animal or in a human?”
Chris - You’ve therefore created not just a potential platform from which we can, in the future, develop full size kidneys but also, quite a useful test vehicle for actually trying out drugs in the future.
Melissa - Yes and I think that’s actually very short term future. We hope to be doing this very shortly. It’s not just using this as a little model of an organ to test for whether a drug is toxic. We can actually make a mini kidney basically to order. There are many patients out there with kidney disease that have mutations. We can make a stem cell from them, we can build a model of their kidney in a dish and actually use it to understand their disease and maybe develop treatments that are more channelled for their kidney disease.