Professor Geoff Raisman, University College London
Part of the show Repairing the Retina and Spinal Cord
Chris - We've looked at the eye, you're working at the other end of the body, on the spinal cord. Why is it such a problem when the spinal cord gets injured, why doesn't it just repair itself?
Geoff - Well there's a number of opinions about that, and the answer is we don't know. But the idea that we have is that the spinal cord attempts to repair itself, but the damaged nerve fibres are unable to grow back.
Chris - It's not that they're just dead?
Geoff - No, it's not that they're dead, in fact they're trying to grow. But the pathway that they need to grow has been destroyed by the injury.
Chris - So what you're saying is that wherever there's a lesion or a cut, or a bit of damage in the spinal cord, this creates some kind of impenetrable barrier that the tiny nerve fibres just can not bridge.
Geoff - Yes. Basically the nerve fibres in the spinal cord run along a kind of pathway cell rather like railway lines or tram lines. And when the damage occurs, these lines are disrupted, they're opened up, and a scar forms which closes off the pathway. So although the nerve fibres have the ability to grow, they're not provided with a pathway to grow along.
Chris - But there are quite a few nerve fibres within the spinal cord, I mean a conservative estimate for just one of the motor pathways is that there's a million fibres in it, so how can you possibly re-lay that pathway for them to be guided where they need to go?
Geoff - Well you can't re-lay the roadway in such a way that everything will grow back. What we are trying to do, and it's only at the experimental stage, (only in animal experiments) is to provide a pathway and see what happens. Now in our situation, what we have found is that less that half a percent of fibres grow back along the pathway that we provide. It sounds very small. But the function that is brought back by that small number of fibres, is very large.
Chris - What's special about that half a percent then? Is there something special about them that mean they're the ones that want to grow and if so do they hold the key to why the other 99.5% wont?
Geoff - Unlikely. What's likely to happen, is that a small amount of signal is carried through by these. A signal is carried across to carry out the function. And the animal, and we hop in future when we do it with people, the person can relearn to use that very small amount of signal.
Chris - But what I'm getting at Geoff is that half a percent of fibres regrow, but the other 99.5% don't. So what's special about the half a percent that enables them to get around this problem, or to grow back? And the 99.5% that don't, why not?
Geoff - It's probably completely random. The pathway's destroyed. Now imagine the pathway was a great 12 lane motorway. We've managed to relay a very small amount of it, a very constrained pathway. So those fibres that are lucky enough to find their way onto it can get through, the rest don't. If we could lay a better bridge than we do, and that's the sort of thing we're trying to do, then you could get even more fibres growing back.
Kat - And what sort of distances are we talking here? When someone for example has a spinal injury, they could just have a very small injury or it could be quite a large crushed area. How far can you make these nerve fibres grow?
Geoff - Now we're talking about experiments in animals, rats, injuries are very small indeed. 1mm. And the fibres will grow across that distance. We do it by transplanting cells, a kind of adult stem cell. We don't have enough cells available to make larger bridges.
Chris - Why do you need to put cells in in the first place, Geoff? Because you said that the scar that's made seems to seal the area and stop these nerve fibres being able to grow through but why do you need to put cells in and what do they do to surmount that problem?
Geoff - Imagine that it's a motorway, a freeway. Travelling over bridges, and half of it falls away in an earthquake. The only way that the cars are going to get across that gap is if you can relay the roadway. Now the roadway in the nervous system is made of living cells. So to repair the roadway you have to be able to transplant the cells in such a way as to bridge the gap.
Kat - So these are more support cells, rather than nerve cells themselves.
Geoff - Yes, they're not nerve cells.
Kat - So you're laying a bridge, really, of these supporting cells, that tell the nerve cells where to grow across.
Geoff - If it was an old fashioned road, relaying the cobble stones. You want the cars to get across it, they're the nerve fibres.
Chris - How do you actually get these cells into the nervous system? Do you have to quite literally open up the entire spinal cord, which is quite a stupendously big thing to do, and then put the cells in where you individually need them? Or are they more intelligent than that?
Geoff - You have to be able to put the cells in the place that you want them. That doesn't mean opening up the entire spinal cord it may mean, for example in our situation, penetrating it with a very fine needle. An injection of sorts.
Chris - So what evidence have you got that this actually works at the moment, Geoff?
Geoff - What we have at the moment is a rat model. And we have shown that with injuries that, for example, impair the use of the limbs, say in climbing or in taking pieces of food, when we transplant the cells the nerve fibres grow back across the injury and those functions come back again. So we can repair this experimental model both anatomically, in structure, and also functionally.
Chris - So if you didn't put the cells in then the rats can't make these limb movements, that function only returns when the cells are put in.
Geoff - The function only returns if you transplant the cells.
Kat - Here's the $64,000 question. How far away do you think we are from seeing this being applicable to humans who've had spinal injuries?
Geoff - Well to answer that let's think of the steps that will have to be taken, and some of which we're taking. The first is, do these cells exist in humans? And the answer is they do. The second is can we get them in a patient in a reasonable way? And the answer to that is Yes, we can get them from the lining of the nose, so we can obtain these cells.
Chris - Why are they in the lining of the nose?
Geoff - Well that's the reason we went there in the first place. As you said, the brain and spinal cord do not repair after injury. But the only nerve fibres which continually repair throughout life in the adult nervous system, are those concerned with the sense of smell. So they have a special roadway, which can repair itself.
Chris - So can you get enough of them to make a repair? Because the human spinal cord's pretty large, the number of nerve fibres in the bridge of my nose is not. Is it possible to get enough of these cells in order to make a decent repair in a human?
Geoff - That's a question we'll have to meet when we get there. But, we are taking these cells from an adult stem cell, which means that it can divide, and in tissue culture, it can make more.
Kat - So you could grow them in the lab, potentially.
Geoff - We do grow them in the lab, unfortunately we still only get a small expansion. Perhaps three fold.
Kat - But if as you say, you only need a very small number of cells to make some kind of functional connection, then potentially that's better than nothing.
Geoff - Indeed. We are hoping to be trying out human cells within the next year or two, in very small injuries of the type where we can hope to get enough cells through a patient. If we can take that step, then we can demonstrate these cells exist in the human, we can obtain them, and they are safe to put in.