Researchers at Harvard and Emoroy University have created an artificial fish that swims using heart muscle cells, formed from human stem cells.
The fish’s tail is covered by two layers of cells, one on each side. When the heart cells on one side contract, the other side stretches out and vice versa.
Stretching one side triggers a contraction afterwards. It keeps the movement going. The rhythm was conducted by a kind of pacemaker.
The fish swam for over 100 days when launched.
Swimmed by himself
The team tested early versions of the fish. Then they stimulated the muscle cells with light, Sung-Jin Park says in a press release from Emroy University. Park began working on the project as a postdoctoral fellow at Harvard’s Paulson School of Engineering and Applied Sciences.
The researchers have previously created an artificial stingray with heart cells from rats that could be controlled with light, wrote Science Alert.
The fact that the fish swam so well by themselves was a coincidence.
– In the beginning, we used light to control the fish’s movements, as we did with the stingray. One day, after finishing the experiment, we stored the fish in the incubator to do more experiments, but we completely forgot that we had saved them, says Park.
After a couple of weeks, the researchers opened the incubator. They discovered that the fish were still moving.
– We found out that the fish swam at their own pace by themselves.
Swimmed faster over time
The researchers found that the stretch on one side opened stretch-sensitive ion channels, which in turn led to a contraction.
Ion channels are tiny tubes in the cell membrane, according to Store norske leksikon. Different ions are transported in different channels depending on which proteins the channel is made up of.
The artificial fish became better at swimming over time as the cells matured. Eventually it could swim at about the same speed as a zebrafish.
– The goal is to build an artificial heart
The fish swam for more than three months. The cells were nourished by the liquid the fish were kept in, writes NPR.
– The really interesting thing about these fish, which we did not expect, is how long they swam and how fast they could swim in the bowl, says Kit Parker, professor of biotechnology and applied physics at Harvard at Harvard University.
The researchers hope that the lessons learned from such experiments will eventually come in handy.
“Our ultimate goal is to build an artificial heart to replace a deformed heart in a child,” Parker said in a press release from Harvard University.
He says that much of the research in this field is about mimicking the anatomical features of a heart or creating heartbeats.
– But here we get design inspiration from the heart’s biophysics, which is more difficult to do.
Biohybrids
In the research article, which is published in Science, the fish are called biohybrids. They are made of both biological and synthetic material.
This is not the first time that scientists have created objects that move using living cells.
In 2020, scientists made small clumps of heart cells and skin cells from frogs, which could move and wander around. According to the researchers, these were the first robots that were only made of biological material, they were called for xenobots.
Makes an imitation of our heart cells
– Here, the researchers use iPS heart cells, says Morten Høydal, researcher at the Department of Circulation and Imaging at NTNU.
iPS cells are body cells, usually from the skin, that are reprogrammed in a laboratory to become stem cells. The stem cells can in turn develop into almost any cell in the body.
– The researchers have reprogrammed the stem cells to mimic heart cells. They turn off on their own, and have the properties of heart cells, says Høydal.
– Why do researchers make an imitation of the heart cells?
– Heart cells are not so readily available. If one is to get it out of man, one must take a biopsy from a human heart. The problem is that it is ethically difficult and impracticable, says Høydal.
An imitation makes it easier.
The fish swim worse in heart failure
– The researchers can take a skin biopsy from a patient who they know has a genetic defect. For example, a heart disease. The message about this error is in the person’s genetic material.
By mimicking the heart cells of a person with a genetic defect, one can study the defect more closely. This is where the biohybrid fish comes in.
– Using a cell from a human who has a heart defect, it will be able to show in the fish. A weakened heart function will lead to the fish swimming worse, says Høydal.
In that sense, such models are exciting.
– Here the researchers can study the cells as a model. Then one can check how medicine works on the cells. Is the hybrid disk getting better or worse at swimming? We thus get tools to both study and treat heart cells. We do this at NTNU as well, says Høydal.
Goes away from animal experiments
– Do you want to be inspired by the article?
– Yes absolutely. Making heart cells from patients is something we will do more of. Whether we make models that look like fishermen is more uncertain.
Høydal points out another advantage of using human cells in the biohybrid fish.
– These are tools that will be important to be able to take steps further in the development of medicines and treatment without animal experiments. It can be more beneficial when we research the human heart, says Høydal.
Reference:
Keel Yong Lee, et al .: «An autonomously swimming biohybrid fish designed with human cardiac biophysics», ScienceFebruary 10, 2022. Summary.