In a first-of-its-kind experiment, scientists have created a fully autonomous artificial fish made out of human heart muscles derived from stem cells, reports a study published on Thursday in Science.
By emulating the contractions of a beating heart, this “biohybrid” fish continuously swam for up to 108 days, a breakthrough that sheds light on cardiac disease and could eventually pave the way toward the development of artificial hearts for transplants. Of course, aside from those worthy applications, it’s also just a completely wild achievement: Franken-fish made out of human heart cells that can swim for over three months. Watch them go!
As mind-boggling as it may seem, this type of experiment is completely in the wheelhouse of the Disease Biophysics Group at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). Led by Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics at Harvard, the group has previously developed biohybrid stingrays and jellyfish from rat heart cells, among other bioengineering innovations.
This time, Parker and his colleagues took inspiration from fish that move by coordinating their body and caudal fin movements to generate propulsion as they swim, such as zebrafish and mollies.
To recreate this motion in an artificial fish, the group layered cardiomyocytes, the muscular cells responsible for heart contractions, on two sides of the biohybrid model’s tail fin. A contraction on one side of the tail produces a stretch on the other; stretch-activated mechanosensitive proteins then kick off a constant closed-loop motion. The team’s electrically autonomous pacing node, which is similar to a pacemaker, keeps a rhythmic clip going so that the faux-fish could keep swimming with the same motion as a beating heart.
To that point, the biohybrid fish were able to swim continuously for an impressive 108 days, logging 38 million beats, far longer than the previous experiments with artificial stingrays and jellyfish, which each moved for about a week. The long duration of these coordinated movements distinguishes the fish as an excellent platform for studying conditions related to the clockwork processes of cardiac activity, such as arrhythmia.
“Our muscular bilayer construct is the first to demonstrate that the mechanoelectrical signaling of [cardiomyocytes] could induce self-sustaining muscle excitations and contractions for extended periods,” Parker and his colleagues said in the study.
“Taken together, the technology described here may represent foundational work toward the goal of creating autonomous systems capable of homeostatic regulation and adaptive behavioral control,” the team concluded. “Our results suggest an opportunity to revisit long-standing assumptions of how the heart works in biomimetic systems, which may allow a more granular analysis of structure-function relationships in cardiovascular physiology.”