Mending a Broken Heart

13 September 2009

Interview with

Professor Sian Harding, Professor of Cardiac Pharmacology at the National Heart and Lung Institute, Imperial College

Ben -   Professor Sian Harding is a Professor of Cardiac Pharmacology at the National Heart and Lung Institute at Imperial College, London and she's here in the studio with me now.  Now, Sian has been using stem cells to develop cardiac patches that could hopefully, one day, be placed on to damaged tissue damaged by a heart attack and basically send in the special cells to repair it.  Hello, Sian, thank you ever so much for joining us.

cardiac muscleSian -   Hello, Ben.  Hi!

Ben -   Now, cardiac repair sounds an incredible ideal that's something that we would obviously want to do. Heart disease is a very common killer.  What are the problems at the moment with cardiac repair?

Sian -   Well, first of all, I should say that there are trials, clinical trials, have been going on for some time using stem cells for cardiac repair and with some success as well.  They've been using bone marrow cells and injecting these into peoples' hearts.  And I think probably 400 or 500 people have been treated that way.  There's one going on in London now with John Martin and good things have happened with these but what appears to be happening is, if anything, a re-growth of blood vessels into the area.  But what appears not to be happening is a production of new actual beating muscle, the myocytes, the muscle cells of the heart. So this is one of the problems and this is what we've been trying to look at in more detail along with any other people about what's the best cell to produce a myocyte.

Ben -   So, although these new blood vessels are obviously a good thing: it'll help to keep heart oxygenated it'll help to keep the muscle that is there healthy.  It obviously won't mean that we can grow back, that we can actually regenerate heart tissue.

Sian -   That's right.  The capacity for the heart to regenerate itself even with these new blood vessels is really very low, especially as you get to the older ages.

Ben -   So, where do you think is the best source for stem cells, if the bone marrow isn't quite doing what we need to do, isn't doing the full job?  What should we be looking at?

Cardiomyocytes derived from the H7 human embryonic stem cell line, © Dr Nadire Ali

Sian -   Well, the frontrunners, the ones that are really good at producing, contracting myocytes at the moment are the human embryonic stem cells and we have used these to produce beating muscle.  It's a very tough muscle. We've kept it in the laboratory beating for over a year in some cases.  You can send it through the post.  It will come out beating at the end.  It's really good tough stuff.  Now, I mean there are problems with this - some people have worried about the ethical problems.  It certainly is a problem about matching it to the immune system of the person.  So there are other possibilities.  One thing is the induced pluripotent cells by looking at what makes an embryonic stem cell an embryonic stem cell.  People have put those factors into skin cells and produced some cells that are really quite like embryonic stem cells and then there are adult stem cells that you can harvest from the heart and expand.  And all these are like coming up on the outside and could be very good but at the moment, they're just potential; whereas the embryonic stem cells are all the ones that are producing the most healthy and hearty tissue at the moment.

Human HeartBen -   It does seem that this is a field of great expansion, an awful lot of new interesting discoveries at the moment because there's a story only a couple of weeks ago about how we might be able to induce stem cells to come out of the waste from liposuction, from just human fat.

Sian -   Oh, yes and I'd be among many other ladies who are very happy with it.  The idea of this source of repair, certainly yes.  So there are lots of other stem cell sources.  Now, the problem we have is that if you have made a cell into a beating heart cell is getting it to the heart.  You can't put it down the blood vessels like you could for bone marrow cells because now they're too large, just block up the blood vessels.  So you have to find another way to do it.  And if you inject it into the heart, I think if anybody's ever seen a heart contract, you can see exactly what's going to happen.  You put a needle in, you inject your substance, your cells, the heart contracts and squeezes it right back at you so you lose a lot of your cells that way.

Ben -   Yes, I'd imagine that could be quite messy.  So you have come up with a slightly more elegant solution of using patches.

Sian -   That's right.  So we want to get some kind of ready-made patch to put to transfer the cells into place.  Most likely, over the scar that happens when you have the heart attack, the infarct scar.  So that's the best place to put it and really now, the interesting part is thinking about what's the best way to get the cells there.  There are natural materials that have sort of porous structure that cells can grow into.  They're one good thing.  But at Imperial College, we have this fantastic materials department and so, we've been trying to make some polymers that have perhaps some added benefits.  For example, one thing we're trying to do is make our polymer match the sort of contractile elastic properties of the heart so it can stop the scar from ballooning out and expanding so you can produce some extra benefit.  While the cells are getting into place and getting ready and growing, you can keep the heart from getting any worse during that time.

Ben - And would you also be able to, as well as attaching your stem cells, can you attach all the different factors that you might need to encourage them to really become part of the existing heart tissue and to develop properly?

Sian -   That's right and one of the benefits of the polymers again or even some hydro gels is to allow slow release of these kind of factors. For example, factors to encourage blood vessels to grow into the cell patch that you've put on or factors to protect the cells. Because if you the patch on when the heart attack has just happened, it's a very hostile environment, very inflamed so you need some kind of inhibitors of that inflammation to protect them.  So even though they are tough, you need something to protect them.

Ben -   It's always nice to hear of a scientific endeavour that is so multi-departmental and you have the material scientists and, obviously, you'll have people working on the medicine side but how-once you've made a patch, how is it actually delivered?  I assume you don't need to be quite as invasive as you would do if you're fully opening up the heart.

CardiomyocytesSian -   Well, in this case at the moment, we are looking at opening up the heart because you need to put it on top of, underneath the pericardium that wraps around the heart.  There are a lot of robotic technologies being developed at Imperial, which have potential for later on.  They're putting amazing things like valves even by robotic technologies.  So there's the potential there, but at the moment, we would need an open-heart surgery.

Ben -   Well, clearly, this is relatively early days.  Where abouts are we at the moment, how far do you think it's going to be before we can really start looking at putting these into people and seeing them actually working out in people on the street.

Sian -   Well, there are parts of this puzzle that have already got into the clinic or have been approved for clinical use.  There's a patch of fibroblasts that can be put on the heart that's been approved.  The human embryonic stem cells have been approved to go into a trial for brain so that's there and so the polymers that we're using are derivatives of ones that are used in other kinds of tissue engineering solutions that have already been put into the body in some form or other.  So, out there, the parts of the puzzle are just getting into the clinic.  It's putting it all together is what we need to do now.

Ben -   Well, this sounds incredibly promising.  It must be a very exciting field to work on as well.

Sian -   Oh, extremely exciting.  There's a new thing for stem cells to do every week, a new way of getting them more things that they can make, yeah.

Ben -   Fantastic.  Well, thank you ever so much for joining us.  That was Sian Harding from the National Heart and Lung Institute, Imperial College, London.

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