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First, science brought us lab-grown meat. Then, it gave us pig-to-human heart transplants. Now, researchers from the Centre for Research and Applications in Fluidic Technologies, or CRAFT, have combined the best aspects of both.
As described in the journal Advanced Biology, they’ve grown a bioartificial model of a human left ventricle – the chamber of the heart that pumps freshly oxygenated blood into the aorta, and from there into the rest of the body – using living heart cells. And it works.
“The unique facilities we have at CRAFT enable us to create sophisticated organ-on-a-chip models like this one,” said Milica Radisic, a professor of cell and tissue engineering and senior author of the paper in a statement.
“With these models, we can study not only cell function, but tissue function and organ function, all without the need for invasive surgery or animal experimentation,” she explained. “We can also use them to screen large libraries of drug candidate molecules for positive or negative effects.”
The model may be small – it’s just a single millimeter long, and half that in diameter, equivalent to a fetus at roughly 19 weeks’ gestation – but it packs a reasonable punch for its size. It can pump blood with a pressure nearly one-twentieth that of a real heart – that maybe doesn’t sound impressive, but it’s enough to pump fluid inside a bioreactor.
And it’s even more exciting when you account for the scale of the model. “Our model has three layers, but a real heart would have eleven,” explained Sargol Okhovatian, a PhD student at CRAFT and one of the co-authors of the study.
“We can add more layers, but that makes it hard for oxygen to diffuse through, so the cells in the middle layers start to die,” she said. “Real hearts have vasculature, or blood vessels, to solve this problem, so we need to find a way to replicate that.”
Still, it’s important to recognize what an achievement this truly is. “Until now, there have only been a handful of attempts to create a truly 3D model of a ventricle, as opposed to flat sheets of heart tissue,” Radisic pointed out.
“Virtually all of those have been made with a single layer of cells. But a real heart has many layers, and the cells in each layer are oriented at different angles,” she said.
It’s fairly easy to grow human cells in a flat petri dish, but in three dimensions, things get a little more complex – so the team had to come up with some rather novel techniques to grow their tiny ventricle. Using biocompatible polymers, the researchers built miniature scaffolds to support the cells’ development in a particular direction. Then, when heart muscle cells are “seeded” into these special structures, they grow together to form a tissue.
In this case, that scaffold was shaped like a flat sheet of three mesh-like panels, the team explained. After about a week of cell growth, the sheet was rolled around a mandrel – a hollow polymer shaft – which created the tube of the bioartificial ventricle.
What’s more, they can even control how fast the miniature muscle beats by applying electrical pulses – and measure the output of the tiny organ. “With our model, we can measure ejection volume — how much fluid gets pushed out each time the ventricle contracts — as well as the pressure of that fluid,” said Okhovatian. “Both of these were nearly impossible to get with previous models.”
So how close is the future of lab-grown bioartificial heart transplants? Well, don’t hold your breath – this is an important proof-of-concept, but it’ll take a long time before you can book yourself in for a brand-new bionic organ.
“The dream of every tissue engineer is to grow organs that are fully ready to be transplanted into the human body,” Okhovatian said. “We are still many years away from that, but I feel like this bioartificial ventricle is an important stepping-stone.”
Not only does the team have to grapple with bioengineering blood vessels for their heart, she explained, but she also hopes to increase the density of the heart cells – that would improve the pumping pressure. And, of course, real hearts rarely have scaffolding inside, so finding a way to reduce or remove that is also on the table for the future.
Still, Radisic says there’s good reason to be optimistic. “We have to remember that it took us millions of years to evolve a structure as complex as the human heart,” she said.
“We’re not going to be able reverse engineer the whole thing in just a few years, but with each incremental improvement, these models become more useful to researchers and clinicians around the world.”
