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First biohybrid fish born from human heart cells created

First biohybrid fish born from human heart cells created

A team of Harvard University researchers, in collaboration with some colleagues from Emory University, have developed the first fully autonomous biohybrid fish. This tiny hybrid fish comes to life from some heart muscle cells derived from human stem cells.

From the biophysical characteristics of the human heart to an artificial fish

The biohybrid fish created in the laboratory is able to swim in a completely autonomous way and its movement recreates contractions of the heart muscle. This could bring researchers closer to their ultimate goal, which is to create an artificial muscle pump that can cure and solve heart problems such as arrhythmia.

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As explained by Kit Parker, professor of bioengineering and applied physics at Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and senior author of the document, the ultimate aim of their research is precisely to be able to create in the laboratory, an artificial heart that can replace a malformed heart or damaged.

Parker also says that unlike what has been done so far in other studies that focus on cardiac imaging as a model, his team is focusing onidentification of the key biophysical principles that make the heart work. And these biophysical mechanisms are the basis of their projects and have been replicated in “a system, a living fish that swims”.

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A biohybrid fish that swims and moves like the heart

The biohybrid fish represents the first autonomous biohybrid device based on cardiomyocytes derived from human stem cells. Its shape and movement are inspired by those of a zebrafish.

This biohybrid zebrafish features two layers of muscle cells, one on each side of the caudal fin. When the muscle on one side contracts, the one on the other side stretches, and this happens thanks to a closed loop system in which muscle lengthening triggers the opening of a mechanosensitive protein channel, which causes a contraction, which in turn triggers the lengthening. This mechanism is in degrees of push the fish for more than 100 days.

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According to Keel Yong Lee, postdoctoral fellow at SEAS and lead co-author of the study, this closed-loop system and the results obtained in the study, “highlight the role of feedback mechanisms in muscle pumps like the heart “.

The researchers also also designed an autonomous stimulation node, similar to a pacemaker, which controls the rate and rhythm of spontaneous contractions of the biohybrid fish. The combined system between the fish musculature and the autonomous stimulation node allowed the fish to perform movements of the fin back and forth, which are also continuous, spontaneous and coordinated.

The road to an artificial heart

As Sung-Jin Park, a former postdoctoral fellow at SEAS and currently assistant professor in the Department of Biomedical Engineering of the Georgia Institute of Technology and Emory University School of Medicine and co-lead author of the study, says, “this new research provides a model to study mechanoelectric signaling as a therapeutic goal of heart rhythm management and to understand the pathophysiology in sinus node dysfunctions and cardiac arrhythmia “.

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Now the research team’s next step will be to build even more complex biohybrid devices, starting with human heart cells. The difficult challenge of the research team will therefore be to one day be able to create something extremely complex and sophisticated like a human heart.

Reference: “A Biohybrid Fish that Swims Autonomously Designed with Human Cardiac Biophysics” by Keel Yong Lee, Sung-Jin Park, David G. Matthews, Sean L. Kim, Carlos Antonio Marquez, John F. Zimmerman, Herdeline Ann M. Ardoña , Andre G. Kleber, George V. Lauder, and Kevin Kit Parker, February 10, 2022, Science.
DOI: 10.1126 / science.abh0474

Ph. Credit: Keel Yong Lee, PhD, Postdoctoral fellow, Disease Biophysics Group, Harvard University (via Twitter)