Making new blood vessels
Your body needs more than just the blood flowing around it. It also needs something to flow through: your blood vessels, or your vascular system. And arterial diseases - where the blood vessels become blocked - including coronary artery disease which causes heart attacks, and carotid artery disease, which causes strokes, are the leading causes of death and disability worldwide. One way to tackle these disorders is to try to unclog blocked vessels, but in some cases the disease is too extensive; in these instances, what’s needed are replacement blood vessels. Adam Murphy spoke to Jo Mountford, at the Scottish National Transfusion Service, who is developing a way to re-grow blood vessels from scratch...
Jo - We’re trying to repair blood vessels that are not working properly, or that have been lost through disease or any other disorders. And in order to do that we're, rather than giving drugs to treat the problem, we're trying to replace the cells that have been lost. So in order to do that we have to grow new cells in the laboratory, or eventually in a clean manufacturing facility, and turn those cells into vascular cells or blood vessel cells. And we're doing that by starting with a population called pluripotent stem cells. And these are a particular type of cell that's similar to those found in the embryo, that are able to make any cell in your body at all. And we have to try and coax them into being just vascular cells and nothing else, so that they can then perform the function that we want them to have.
Adam - How do you make it turn into a vascular cell and not say, a brain cell, or a muscle cell?
Jo - Yeah that's the really tricky bit. So that's why we, to begin with, always struggle, and where we have to devise new protocols and new processes for doing this. We take our cues from developmental biology, so we understand how the vascular system and all of the other organs form in an individual during, you know, embryology and as a person grows, and by understanding how that biology works, we then have to try and make that happen in a dish in the laboratory.
So we deliver what are called growth factors. So these are small proteins that deliver signals to the cells, and they specifically tell the cell to, for example, turn into a vascular cell and not a bone. And also we support them with growth media. So this is the liquid that they grow in. It contains proteins, sugars, salts, all of those things. And it effectively is the nutrients, but also it can be selective. So only certain types of cells will grow in certain types of media. So if we use a vascular media those cells will preferentially survive and other cells like bone or brain cells for example will die off.
Adam - And how do you end up with something that is a blood vessel and not just a clump of cells?
Jo - These cells are programmed by nature of the fact that they're endothelial cells, vascular endothelial cells. They're self programmed to know what to do, if you like. So as long as they're in the right environment they will regulate and organise themselves to form tubules. And they'll attract other cells from the periphery to form muscle layers, to form the bigger vessels for example, so you end up with a multilayered blood vessel.
Adam - And when you've got your cells grown, how do you put them into subjects?
Jo - So again, it's pretty simplistic, in our model systems and eventually hopefully in human trials, we're going to look at areas of the body which ischemic, so they have very poor blood supply or compromised circulation. So what we're going to do is directly inject into those areas of poor circulation, and the intent is there, that the cells we put in will either form new vessels themselves, or that they will encourage the cells that are already there and perhaps dormant, or not working properly, to buck up their ideas, if you like, and to regenerate or to restore function themselves. So direct injection and then either they make the vessels or they incorporate into, or encourage vessels that were already there to regrow.
Adam - Are there any particular conditions you're targeting that this could help with?
Jo - Yeah so our first indication is actually one that's really quite common, so it's peripheral arterial disease or critical limb ischemia is the final stage, and this is where particularly in the leg, you get compromised circulation, and the final stage of the actual treatment for it is amputation. So we'd hope that you could treat the disease earlier and avoid those very late stage complications.
Adam - What stage are you at now?
Jo - So that's a really good question, and we're at the stage which is always the difficult one for these type of projects. We have all of the efficacy data that we need, so from animal models for example, so we know that this therapy works in the systems we've looked at it. We're now at the point of needing to go to clinical trial in humans, in order to do that we need funding. And the first step of that is to manufacture the cells in a manufacturing environment that's qualified and regulated to do so, so to produce them at a sufficient grade and clean enough and safe enough. And then we'll have to do safety testing and then we can go to human trials.