First, science brought us meat from the lab. Then we had pig-to-human heart transplants. Now researchers at the Center for Research and Applications in Fluidic Technologies, or CRAFT for short, have combined the best aspects of both.
As described in the magazine Advanced Biology, they have grown a bioartificial model of a human left ventricle – the heart chamber that pumps freshly oxygenated blood to the aorta and from there to the rest of the body – using living heart cells. And it works.
“The unique facilities we have at CRAFT allow us to create sophisticated organ-on-a-chip models like this one,” said Milica Radisic, Professor of Cell and Tissue Engineering and senior author of the article in a expression.
“These models allow us to study not only cell function, but also tissue and organ function, and all without invasive surgery or animal testing,” she explained. “We can also use them to screen large libraries of drug candidates for positive or negative effects.”
The model may be small – it’s only a millimeter long and half the diameter, which is equivalent to a fetus at 19 weeks gestation – but it packs a decent punch for its size. It can pump blood at a pressure almost one-twentieth that of a real heart — that might not sound impressive, but it’s enough to pump fluid into a bioreactor.
And it’s even more exciting when you consider the scale of the model. “Our model has three layers, but a real heart would have eleven,” explains Sargol Okhovatian, a PhD student at CRAFT and one of the study’s co-authors.
“We can add more layers, but that makes it harder for oxygen to diffuse, so the cells in the middle layers start to die,” she said. “Real hearts have a vasculature or blood vessels to solve this problem, so we need to find a way to replicate that.”
However, it is important to recognize what an achievement this really is. “Until now, there have only been a handful of attempts to create a true 3D model of a ventricle, as opposed to flat sheets of heart tissue,” Radisic pointed out.
“Virtually all 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 shallow petri dish, but things get a bit more complex in three dimensions – so the team had to develop some pretty novel techniques to grow their tiny ventricle. Using biocompatible polymers, the researchers built miniature scaffolds to help cells develop in a specific direction. When heart muscle cells are then “seed” into these special structures, they grow together to form a tissue.
In this case, that scaffold was shaped like a flat slab of three mesh-like panels, the team explained. After about a week of cell growth, the foil was rolled around a mandrel – a hollow polymer shaft – creating the tube of the bioartificial ventricle.
In addition, they can even use electrical impulses to control how fast the miniature muscle beats – and measure the performance of the tiny organ. “With our model, we can measure the ejection volume – how much fluid is ejected with each contraction of the ventricle – and the pressure of that fluid,” Okhovatian said. “Both were hardly achievable 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 will be a long time before you can sign up for a brand new bionic organ.
“The dream of every tissue engineer is to grow organs that are completely ready to be transplanted into the human body,” Okhovatian said. “We’re still many years away from that, but I believe that this bioartificial ventricle is an important stepping stone.”
Not only does the team have to deal with bioengineered blood vessels for their hearts, she explained, but they also hope to increase the density of heart cells — which would improve 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 won’t be able to 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.”