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Artificial “Fish” Made From Cardiac Cells Swims Like A Beating Heart

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Stephen Luntz

Freelance Writer

clockFeb 10 2022, 19:00 UTC
biohybrid

This fish is all heart, except for the bits that are gelatin, paper, and plastic. But it's the human heart cells that make it swim autonomously. Image Credit: Michael Rosnach, Keel Yong Lee, Sung-Jin Park, Kevin Kit Parker

If you can't make an artificial organ, making a whole animal seems like a stretch. Nevertheless, researchers working on artificial hearts have created a biohybrid “fish” from human heart cells as a stepping stone. Its zebrafish-like motion is powered by heartbeats. One day, it may save the life of someone you love.

The shortage of donor organs is so severe people are genetically engineering pigs to produce hearts humans can use. A team at Harvard University are working on a different approach, seeking to build artificial hearts out of cardiac stem cells.

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They're a long way from that but took a diversion to turn the cells into a fish-shaped biohybrid creation and see if it would swim. In Science, they report success – they have made the first-ever autonomous biohybrid device from human stem-cell derived heart cells.

“Our ultimate goal is to build an artificial heart to replace a malformed heart in a child,” said Professor Kit Parker in a statement. “Rather than using heart imaging as a blueprint, we are identifying the key biophysical principles that make the heart work, using them as design criteria, and replicating them in a system, a living, swimming fish, where it is much easier to see if we are successful.”

The creation is called a biohybrid because it combined human cells with non-biological material such as a gelatin and paper body and a plastic floater. No material from an actual fish was incorporated.

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The key feature of a heart, after all, is that it beats, and its constituent cells do likewise. The team had 73,000 stem cells turn into cardiac muscle cells and painted them onto a structure shaped like a zebrafish, with two layers of muscle cells on each side of the tail fin. The muscles on each side contained retinal proteins sensitive to different colors of light. By alternating light colors, the cells were made to beat out of sync, so that one side contracted as the other stretched, pulling the tail first one way then the other. Red fish, blue fish indeed.

The motion pushed the “fish” forwards, and the team have demonstrated the cells can maintain this motion for 108 days when swimming in a glucose-enriched salt solution.

Schematic of how the biohybrid fish swims. Image credit: Michael Rosnach, Keel Yong Lee, Sung-Jin Park, Kevin Kit Parker

“By leveraging cardiac mechano-electrical signaling between two layers of muscle, we recreated the cycle where each contraction results automatically as a response to the stretching on the opposite side,” said co-first author Dr Keel Yong Lee. The frequency and rhythm of the beat is controlled by a pacing node, giving the team practice in making a pacemaker counterpart.

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The fish evolved from previous projects of the same lab, modeled first on a jellyfish and then on a stingray. However, both of these used rat heart cells whereas the as-yet-unnamed fish is our flesh and blood. It's also a much better swimmer that lasted a lot longer thanks to the double pacing mechanisms.

Perhaps most remarkably, the biohybrid got better at being a fish as time went on. The exercise of swimming strengthened the cells, producing faster swimming speeds and improved muscle coordination over the course of the first month.

None of this means we are about to see stem-cell hearts pumping blood in living people any time soon, but Parker considers it progress, saying: “I could build a model heart out of Play-Doh, it doesn't mean I can build a heart. You can grow some random tumor cells in a dish until they curdle into a throbbing lump and call it a cardiac organoid. Neither of those efforts is going to, by design, recapitulate the physics of a system that beats over a billion times during your lifetime while simultaneously rebuilding its cells on the fly. That is the challenge. That is where we go to work."

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And remember, if a bad break-up has made it feel like your heart is broken, there are plenty more fish in the sea.


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