Keeping hearts alive outside the body

Cardiologist James Rudd takes this question...

James - Yes, it's a very good question, Chris. And I should say that around 200 heart transplants take place in the UK every year, but unfortunately over a thousand people a year die on the waiting list because they just can't get a suitable donated heart in time. Now the current method of taking hearts out of donors is that the heart is placed into an icebox where it is stored, and then the icebox is transported to the person who needs the new heart. Now the way of doing it using the icebox means that the heart stops beating because there isn't any blood supply. So the heart itself immediately starts to deteriorate and the heart cells die. It is cooled down using ice, so this offsets the deterioration to a certain extent, but still the heart needs to be implanted into the person within about three to four hours. So that limits the geographical range that hearts can travel from recipient to donor. There's a new technology which has been around just for a couple of years already called heart in a box. And that's a method of transporting donor hearts that allows them to survive up to eight hours outside the body. And the way it works, again it's a lunchbox-sized device, but this time the heart keeps beating once it's outside of the donor's body. It actually uses a similar technique to a heart-lung machine where the donor's own blood supplies the heart muscle with oxygen and glucose, and also immunosuppressant drugs which keep it beating and keep it in the best condition before it's implanted into the patient. And that can extend the time out to around eight hours. Machines are expensive, about 150,000 pounds, so they're not used in every case. But experts believe that that will increase the number of organs available by about 50%, so many more of those people on the transplant waiting list will hopefully get something in time.

Chris - I was also talking to the surgeons who do transplants of other offal organs, things like livers for example, kidneys; and they were testing devices so that you can rest an organ and give it a circulation for a while before you transplant it. And they were finding when they did this, they could get some organs to recover to a stage where you would then - have previously rejected them - you would then instead aacept them and say, "well that's good enough to transplant." And it would appear that instead of it having had a shock of having been taken out of a donor and then have the shock of going into a new patient, by resting it in a controlled environment for a little while beforehand, it enables it to regenerate a bit.

James - Yeah. I think that's very similar to the way that this is done. So organs that, we call them marginal organs, that might have been a little bit not good enough to be transplanted can now become available to a wider pool of people.

Chris - Yeah. Of course one other aspect of this is relevant to your field of immunology, Clare, and that's actually organ rejection, isn't it? Because one of the big challenges is finding organs that are a match. So when people talk about that, saying "I'm looking for a match", what do they actually mean by that?

Clare - So effectively what you're trying to do is to make sure that the organ matches the tissue in the immune environment of the patient to whom the organ is going to be donated. And so there are various ways you can do that. There are various molecules, you can look at different tissue types, and find somebody who's got an immune system and tissue that's as close to the immune system of the recipient as you possibly can. So that's why there are organ donor registers and so forth. So it's a central part. But what you also do is you put your patients on immunosuppressive drugs, which actually dampen down the immune system. So you're giving it the maximum chance, you have a tissue type that is closely matched between the donor and the recipient, but you also suppress the immune system so it doesn't attack the organ when it goes into the body.

Chris - There must be consequences of damping down the immune system like that though. Because we have an immune system for a reason.

Clare - Yeah, yeah. There are massive consequences. So the biggest problem is, well, one of the biggest problems is trying to protect your patients then from getting infection. So whereby a cold is normally something that one can fight off quite easily, if you're a patient on immunosuppressive drugs, particularly early on after a transplant when you're on particularly high doses, then you're at serious risk and you need to avoid people who've got colds and various other relatively harmless ailments to a greater degree. Because this can cause a serious, serious problem in these patients.

Chris - Why can't we reprogram the immune system to say... because it obviously had to learn in the first place that your heart is part of you, and to regard it as friendly; why have we not been able to reprogram the immune system to say, "James has kindly given you his heart, Clare, this is your friend. Don't reject it."

Clare - Yeah. We're moving towards being able to think about these things all the time, as we understand how 'foreign' and 'self' is seen within the body, and what the molecular biology behind those processes are. And we have processes such as gene transfer, gene editing, the CRISPR-Cas9 systems. They are all ways in which we can potentially change organs and change cells within organs such that they are more familiar to the immune system of the person that they're going into. But we're a long way from that at the moment.

Chris - Fran?

Fran - So related to that, why is it that if a woman is pregnant, her body doesn't reject the baby as foreign tissue, but if the baby then grows up and donates an organ to her, that could still be rejected? What happens over that period? And could we use it to help?

Clare - Yeah, I mean there's quite a lot of changes that go on when somebody is pregnant. So they actually become semi-immunosuppressed and that helps to protect the baby. And of course a baby is not necessarily going to be a good donor for a mother because the baby has the father's DNA as well as the mother's DNA, so it depends how much of the mother's immune system and how much of the father's immune system, and the complex recombination, because the genes that are present in the father and mother in the immune system can also mix and match. So it's a complicated process.

Chris - It's also interesting that certain diseases of the immune system, autoimmune diseases, where the immune system attacks a tissue that it shouldn't do become much more common after a woman has had a baby. And people have pointed out that if you go hunting through a woman's body you can find, after she's been pregnant, examples of her baby's cells that have come out of the baby, gone round her bloodstream, and then taken up residence in certain tissues. For example the thyroid, people have done this showing if a woman has had a boy baby, there's no way she would ever have a Y-chromosome in her body. But after she's been pregnant you can find cells with Y-chromosomes in them in some of her tissues. And the suggestion is that after the baby is born and the immune system gears itself up to full strength again, then you get these autoimmune problems because all of a sudden the immune system starts to see these foreign cells sitting there in the host tissue that shouldn't be. And then you get a reaction.

Clare - Absolutely. And you've also reverted the hormonal status of the person, because things like progesterone are very, very - which is what's produced during pregnancy - is a fantastic immuno damper. And as soon as you bring oestrogen back in, which soups your immune system back up, then off you go and anything foreign is going to trigger a reaction. So yeah, it is very interesting.

Chris - The immune system's an amazing thing, isn't it? And it's one of those things we just don't have really much of an insight into really what it's really doing. We vaguely understand, at a sort of broad level, but we really don't understand the intricacies, do we yet?

Clare - One of the exciting things now is that we're really moving much, much further into understanding what the individual cells do and the plethora of cells, and there are different subtypes of sales, which makes life very complicated. But also as we look at patients of various rare diseases where they have to find mutation in different immune genes, then we're beginning to use that information to understand what the immune system does. But there is a long way to go.