David Kent, Cambridge Cancer Centre
We currently face a blood shortfall, so why can't we just grow some blood in a lab? Chris Smith spoke to David Kent, from the Cambridge Stem Cell Institute, who is aiming to do just that. His idea is to harness the bone marrow stem cells that normally produce blood in the body and use them to make tailor-made blood products for each individual...
David - Blood stem cells are very rare cells in the adult bone marrow and they are ultimately responsible for the production and destruction of trillions of blood cells every day. So, quite potent cells, but as I said, quite rare, so difficult to find in adults, but when you can find them and you can manipulate the way they make decisions then you can start going down and making all of the different mature cell types in a blood system. So, all the red cells and platelets that are so desperately needed in the blood donation clinics.
Chris - You make it sound very simple. What's the stumbling block?
David - The big stumbling block is that there are many, many cell intermediates that these cells have to go through before they come from a stem cell all the way down to a very mature red cell.
Chris - You mean, they start off as sort of "baby cells" then they grow up into adolescent cells, and then eventually become young adults and then mature adults - that’s where we want them, at the mature adult stage - but you’ve got to shepherd them through all those stages first?
David - Exactly and understanding teenagers, as we all know, is very difficult. So, trying to figure out what proteins are really directing the fake choices is what our lab really focuses on. And so, we try to understand at a single cell level how individual stem cells are making the decision to make a new stem cell or maybe go off and make one of the many different types of the blood system.
Chris - Is it just the way the cells talk to each other and how they send messages amongst themselves with protein signals and so on that’s important, or is the physical environment itself important because obviously, when we look at the bone marrow, it’s a 3-dimensional environment. You’ve got cells touching each other and communicating in 3 dimensions. A culture dish is often just two...
David - Yeah, absolutely and there are many groups sort of attacking this problem from many different ways. But on the bone marrow itself, there's a specialised area called the bone marrow stem cell niche and this niche is this place where all of the bone line in cells and all of this supportive cell types that feed the stem cells are located. There's been enormous amount of work on that. But in a culture dish, you can actually start to create these 3-dimensional micro environments as well. And so, there are many groups that have actually started to try and mimic what goes on in a bone marrow micro environment.
Chris - If you do that, do you start to get these stem cells to turn into the kinds of cells that we would need to produce – I don’t want to say fake blood – but artificially produced personalised blood?
David - That would be one of the ultimate goals, is to really understand how a single cell makes that entire journey to mature red cells or mature platelets. There are also groups that are trying to do this even with the knowledge that we already have. So, we don’t understand everything completely, but trying to give a best push at it. There's been some serious progress made. But the amounts required in an individual transfusion are quite enormous and scaling this up has been the big problem. So, that actually requires bioengineers to be thinking about things as well as biologists to really try and understand how we make blood products for everybody from these stem cell populations.
Chris - I read somewhere that it’s about a million million cells every day that your bone marrow has to replace which are continuously just being thrown away because they’ve got old. So, we have to come up with a culture dish capable of the same incredible turnover that your bone marrow does.
David - Right. So, what we'd tried to do I guess in an ideal world is put in the sort of teenager cells so we wouldn’t have to put in that enormous number of cells. We’d put in cells that could create that enormous number of cells over the lifetime of an individual. So, similar to how stem cell transplants work, when somebody has a full bone marrow transplant, the stem cells go in and setup shop as if they were indeed the local resident cells. And so, if you could get some sort of intermediate there, I think that would be quite a good way to go.
Chris - I suppose one problem is that when people come to hospital and they're acutely, urgently in need of blood transfusion, there wouldn’t be time to do this. This is something longer term. So, you would presumably need to take from me a sample of my bone marrow in order to start your process and you're going to have to scale that up but in the meantime, I'm still going to need blood from somewhere.
David - Right and so, I guess the middle ground solution in that case would be to make unlimited supplies of A blood cells, AB blood cells, O blood cells, etc. and so, you can take individual donors, scale those processes up, make the mature cell types, store them all down so you have banks of blood cells that are made in this way, but not individually transfused back into the same person. So, you wouldn’t have the need to wait that period of time outside the body.
Chris - Are we far away? How long do you think before we see on the shelves, blood that’s tailor-made to an individual?
David - Well, I would say, in my own career, the rapidity with which sciences progress has been incredible especially in the stem cell field. And so, I think anything is possible but we’re certainly 5 to 10 years away from seeing anything that’s in a patient I think.