"Science" Harvard University made a hybrid 'mermaid' out of human heart cells

On February 11, 2022, a research team from Harvard University and Emory University, inspired by the shape and movement posture of zebrafish, used human stem cell-derived cardiomyocytes to grow a fully autonomous biological hybrid fish for the first time.
Can swim independently for 108 days
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The research results were published in the top international academic journal "Science" with the title: Autonomous swimming biological hybrid fish designed using the principles of human heart biophysics
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Using this autonomous swimming biohybrid fish to focus on key regulatory features of the human heart, the researchers uncovered the importance of the feedback mechanism of myocardial pumping
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The research team also said the discovery could help in the future to develop artificial hearts made from living cardiomyocytes to treat patients with severe defects in cardiac muscle function
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Design and construction of biological hybrid fish

In the circulatory system, electrical signals and cardiac automatism play a crucial role in regulating the speed and strength of cardiac muscle contractions
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Autonomy of the heart originates from the sinoatrial node, which is structurally and functionally isolated from the surrounding myocardium and spontaneously initiates electrical activity in the absence of external stimulation and direct neural intervention
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The researchers then used the principles of the heart-controlled system to design a biological hybrid fish that could make a fluid-pumping system comparable in efficiency to that of natural fish
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This biohybrid fish possesses antagonistic muscle bilayers and geometrically insulated cardiac tissue nodes containing human stem cell-derived cardiomyocytes (CMs)
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To replicate the electrically insulating structure of the SA node, they created an electrical connection between the SA node and muscle tissue through an outlet channel
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Thus, the muscle bilayer and G-node of the biohybrid fish together allow it to generate a continuous rhythm to regulate muscle antagonism, resulting in spontaneous, coordinated body caudal fin movements
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Optogenetically induced pattern of body trunk-caudal fin propulsion

To systematically characterize the kinematics of the muscle bilayer, they controlled antagonistic muscle contractions in biological hybrid fish by external optogenetic stimulation
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Spontaneous rhythmic contractions that drive movement

Next, they tested whether antagonistic muscle contractions reconstituted by human stem cell-derived cardiomyocytes could maintain spontaneous rhythmic contractions through mechanoelectronic signaling
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It was found that spontaneous activation and contraction on one side of a biohybrid fish can lead to subsequent antagonistic contraction on the other side through mechanical coupling between muscle tissues
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These spontaneous antagonistic contractions cause the fish to move forward in a rhythmic alternating bending motion
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Long-term performance of biological hybrid fish

Given the spontaneous antagonistic muscle contractions in biohybrid fish, it is inevitable that some will question whether this spontaneous activity can be effective in the long term
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In the end, the researchers allowed the biohybrid fish to move spontaneously for 108 days, the equivalent of 38 million heart beats
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The results showed that the autonomous swimming biological hybrid fish continuously improved muscle contraction amplitude, maximum swimming speed and muscle coordination within 1 month, and maintained good swimming performance for 108 days
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These data demonstrate the potential of the muscle bilayer system and electrical signaling as a means to promote muscle tissue maturation in vitro
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Research summary

In conclusion, the researchers took design inspiration from the biophysics of the heart and used human stem cell-derived cardiomyocytes for the first time in the world to create this autonomous biological hybrid fish that can swim continuously for more than 100 days
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By building a "heart" yourself to replicate key biophysical principles in how the heart works, it could help study heart disease in greater detail in the future
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As a next step, the team aims to create more complex biohybrid devices using human heart cells
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Professor Kevin Kit Parker, corresponding author of the study, said: "Our ultimate goal is to build an artificial heart to replace a deformed heart in a child
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