Prof Alison Lloyd, University College London
Thanks to the dexterity of surgeons, itís possible to reattach severed fingers, toes and even limbs - and whatís even more amazing is that the peripheral nerve cells, or neurons, can rewire themselves back into the damaged tissue, bringing back sensation and movement. But how do they do it? UCLís Alison Lloyd has been studying how these neurons, along with special helpers called Schwann cells, manage this impressive feat, as she explained to Kat Arney..
Alison - Imagine that your nerve is completely severed. The connections to the nerve, if you could think of it like an electrical cable with lots of separate wires within it, attaching to various points, downstream of that cut, all of the wires will disintegrate. Then what has to happen is those wires or those neurons have to regrow back to their targets and thatís the repair process. This is much more tricky than it sounds but itís joined up by this sort of mush of inflammatory cells and matrix which joins together the ends of this severed nerve.
Kat - Sort of biological gluey stuff.
Alison - Exactly. Itís very non-directional and itís very dense, full of matrix and other cells. What weíve shown previously is that a special cell type within the nerve which are called Schwann cells, they are able to migrate out of the stumps across the bridge and they migrate as cords across the bridge taking the axons with them. They are then able to grow down back to their targets. So, what the mystery was, what we didnít understand is, this is quite a big gap. This is quite a big bridge. There was no directionality to it. We couldnít understand how these cords knew where to go. What we found was that there was another cell type that was very important in this process. These are endothelial cells and these are the cells that make blood vessels. So, what was happening first was that this mush had cells in it which were sensing that they werenít getting enough oxygen, what happens in response to loss of oxygen that there are signals that make blood vessels grow.
Kat - What do your results show might be going on when nerve cells are growing across this gap to repair the damage?
Alison - What we found is that the Schwann cells are only able to migrate along the surface of another cell type. In this case, itís the blood vessels. So, the first thing that happens within this bridge is that there's a lack of oxygen which is sensed by inflammatory cells. They send out a signal which causes the formation of blood vessels. The Schwann cells can't migrate within this matrix. They need this surface of the blood vessel. The blood vessels grow as tracks. They're polarised in the direction of travel and the Schwann cells use this to find their way across the bridge.
Kat - So, itís kind of like a train can only run on a track. Yeah. Once it gets going, itís great but it has to have that track there first.
Alison - Yes. So the Schwann cells seem to have this engine that can make this forceful migration, but they need a specific track in order to migrate and thatís different to other cells.
Kat - How can we use this knowledge to, for example, get better at repairing nerves?
Alison - We have surgeons who tend to sew up the gaps, but even so, for serious injuries, there's often a gap in the nerves. And so, people try and make artificial bridges to encourage this nerve growth. And thatís a big problem area in that, sometimes the gap is quite big and then you have these different artificial bridges that people try and use to encourage the neurons to regrow across this bridge area. And so, I think what our work suggests is that what you want to do is to mimic the real bridge. So, you want to maybe make tubes with blood vessels, either blood vessels themselves or surfaces that mimic what it is about blood vessels that provide a surface for the Schwann cells. But I think it has broader implications for other diseases as well. The way that certain cancers spread within the body, these cells are moving along the surface of other cells. It has been observed that cells such as melanomas and gliomas for example.
Kat - Those are brain tumours.
Alison - They're brain tumours and they're very, very invasive. Thatís the major problem with them but they also seem to be migrating along the surface of blood vessels. So, itís possible that when these cancer cells are moving and they're moving along blood vessels, they're using the same mechanisms that you see following an injury and theyíre co-opting this type of behaviour in order to spread. And so again, if we can understand that better then possibly, we can understand better how tumours spread and then maybe do something about it.