Grown brain tissue transplant success

Up first this week, there's renewed hope for the millions of people affected by brain injuries and degenerative diseases: scientists have successfully grafted new lab-grown brain tissue into the brains of rats and shown that the new tissue wires itself into the host brain and responds electrically to signals from elsewhere in the animal's nervous system. Although scientists have demonstrated over many years that new cells can be added to the brain, this is one of the first studies to show that the implanted tissue can grow, develop a blood supply and connect functionally. Neurosurgeon Isaac Chen, from the Uni of Pennsylvania started by using human blood stem cells to grow mini brains called organoids in the lab, which he then transplanted into recipient rats...

Isaac - An organoid is basically something we make in the lab that resembles the organ that it's supposed to look like. So, for instance, there can be lung organoids, intestinal organoids, kidney organoids, and in our case, what we're looking at were brain organoids that we form from stem cells that we can get from the blood of any human being. We give it a recipe of different growth factors and other things in the media that allow it to become something that looks like a mini brain.

Chris - And when you do this - because brain tissue it's a complicated tissue, it's not just nerve cells, there's a whole assemblage of different cell types in there - you get something resembling a piece of brain with all the right cell types?

Isaac - You get a lot of the different cell types. It's actually quite amazing the diversity of cell types that you are able to create. And it's not a perfect replica of the brain, but it's as good as we can do right now with the technology that we have, which is why we chose to look at this as what we transplanted.

Chris - And how did you transplant it?

Isaac - I'm a neurosurgeon, so I've been able to train my lab to do brain surgery on rats. What we did first was we took a piece of the skull off, used simple vacuum suction to create a hole in the brain, we took an organoid and we gently laid it within that hole in the brain and then we close things up.

Chris - So you end up with human brain tissue in this cavity you've made in the recipient rat brain. Presumably you were able to follow up these animals for a period of time afterwards to see what the tissue did?

Isaac - That's right. So we went out to upwards of three months after we did the transplantation of the organoid. And we were specifically interested in looking at how the neurons of the organoid those nerve cells are able to integrate with the brain of the animal, both structurally as well as functionally. We did a variety of experiments to look at those aspects of integration.

Chris - Are they actually wiring themselves in because that's the sort of the thing you're testing effectively, isn't it? Is this becoming a meaningful brain area that can contribute to brain function?

Isaac - Yes. And so that's what was really cool about the work. We were looking at whether or not the neurons got wired in, in a couple of different ways. We were able to use a modified virus to look at connections between the organoid and the brain. In a really cool experiment that we did, we injected a virus into the eye of the animal and we were able to show that there was a direct connection, a pathway that formed between the eye of the animal and the organoid that we had transplanted. So that gave us evidence that there was a structural connection between the visual system of the animal and the organoid. The eye is actually part of the brain, and so it was really cool to be able to see that the eye was directly connected with the organoid. The other thing we ended up doing was to stimulate the animal with different types of flashing light and other patterns of light, and seeing what types of electrical responses were present in the organoid itself. And we found that there were very specific electrical responses that showed up in the presence of the stimulation. And so this gave us a sense that there was a functional connection between the organoid and the animal's brain as well.

Chris - And presumably the reason you are interested in doing this is that in human brain trauma or because of degenerative conditions, the best way to remedy that is to put new tissue back. And this is the first step really to testing, if we make and engineer tissue in a dish as a replacement, can it actually be meaningfully implanted into the brain and have some prospect of surviving and contributing to brain activity?

Isaac - That's right. Our brains are not able to do a lot to repair to itself after some sort of an injury, which is why patients with brain injuries and strokes and other types of conditions have neurological deficits. So yes, this is start of the road to try to understand, can we create something in a lab, some sort of a tissue that resembles the brain that we can then insert into the brain of a patient with a problem and be able to allow them to restore function?

Chris - Rats are obviously not humans, they're also much smaller. And if we're talking about the size of a human brain and the size of a likely implant you'd need to fix a damaged bit of brain, we're talking about possibly an order of magnitude or more of scale up. Do you think this will work if we were to try and scale it up in that way in a human?

Isaac - There's a lot that we have to figure out before we're ready to proceed with something like this in a patient. But there is a path that I can foresee where we do not necessarily need to scale up the tissue itself. There are parts of the brain where it's structured like a lot of repetitive processors. And in this case, by inserting smaller clumps of tissue, you could be adding processors to the brain in very specific areas where it's been damaged. And you don't necessarily have to replace the whole cavity, let's say, of a stroke or an injury, a brain injury, something like that. But you could insert smaller pieces of tissue that can effectively increase the computational capacity of that particular area of the brain. And because we understand the brain more and more as a network, these smaller fixes might be able to improve the function of that brain to the point where there's recovery of function for the patient.