Lab grown mini hearts that beat
In a world first, scientists at Vienna's Institute of Molecular Biotechnology have managed to grow miniature hearts from stem cells in a laboratory culture dish. The key, according to Sasha Mendjan who led the work, is adding the right growth signals at the right time. This results in clusters of stem cells organising themselves into a hollow chamber with an inner and outer lining, and heart muscle cells that beat. It's early days, but this will enable researchers to study the basis of some common heart diseases, and ultimately takes us a step closer to growing a new heart from scratch, as Sasha explained to Chris Smith…
Sasha - What we are looking at is essentially a chamber-like structure, or heart 'left' chamber. And we essentially managed to recapitulate its development - how it develops from a stem cell-like state - which we find also in the human embryo.
Chris - You mentioned the embryo - the heart's actually one of the first organs to form, isn't it?
Sasha - Yes. It's the first organ to form; it already starts beating on day 23 of human development, which is a stage of development where we cannot even look at really in detail. This is when we know that congenital heart defects arise, and they are quite common - about 2% of all children that are born have one. But what is even more important is that these developmental mechanisms are also very important later on for disease, for example for regeneration or their response to injury, how our heart grows, and also how our heart fails. All these developmental mechanisms are involved.
Chris - You've done this from stem cells. People have used stem cells to build cardiac, and also blood vessel tissue, in dishes before to do this sort of thing. So what's different with what you've achieved?
Sasha - The difference is that we managed to figure out how we can add specific molecules to the media where these stem cells grow and tell them how to build a heart by themselves. This is how our organs develop. And this is what now, for the first time, we've managed to do with the human heart. What people previously managed to do is to instruct the cells, the stem cells, how to form different cell types that we find in the heart like the muscle cells or the cells of the vasculature. But what they didn't figure out is how to form the whole structure.
Chris - Can you talk me through, then, the entire sequence of experiments - what you do, with what, in order to make this happen?
Sasha - We put our stem cells into a plate that has 96 wells. And then in each well, one of these cardioids - as we call them - starts developing as we give the cells the instructions. Essentially we are giving them molecules at very specific times during a time course of about seven days. And these molecules tell the cells, "okay, I need to build a chamber that is beating, that has an inner lining as a real heart would have, and also an outer layer as a real heart would have." And this is what we achieved.
Chris - And the molecules that you put in - they're sort of growth factors or chemical cues that are the nudges that tell the cells, "now do this, now do this"?
Sasha - Exactly. They are proteins that will bind certain receptors on the cells and will signal. We call them signalling molecules. And this is exactly what we do.
Chris - And when you look at these mini chambers - these cardioids, as you're dubbing them - down a microscope, do they look like... if you were to take a piece of heart out of a developing embryo, it would really look like that?
Sasha - Yeah! This was exactly the amazing thing. The first time we saw it I just couldn't believe it, because this is exactly how an embryo in a heart would look like. It's hollow, it's this beating chamber. It was quite amazing to look at together with the students.
Chris - Now you know how to do this, what can you do with it? What are the applications?
Sasha - The main application - we could recapitulate a genetic defect of the heart where the development of the chamber is impaired. This is related to the probably most severe genetic defect you can have actually in children that affects the heart, which we call hypoplastic left heart syndrome. And there, basically the whole left ventricular chamber of the heart gets obliterated, and these kids need surgery within a week otherwise they will die. And now, really for the first time, we can start looking into the mechanism of that particular congenital defect.
Chris - Would you do that by taking stem cells from children who have that disorder, or a family history of that disorder, and using their stem cells - so the heart, the cardioid, that develops in your system, essentially looks like a mini version of what happens in reality?
Sasha - Exactly. So this is what our next step is going to be now. We are going to take cells from these patients, reprogramme them into the stem cell state, and then we're going to try to re-enact, recapitulate the disease, what happened, what went wrong in these kids. And then that of course means that maybe we can also try to find a way to either predict this or figure out why is this happening, etc. Because as I said, cardiac defects are much more common than other defects and we don't really know why.