Human Cells Transformed Into Tiny Biological Robots

The multicellular bot moves around and helps heal “wounds” caused to cultured neurons.

Researchers at Tufts University and Harvard's Wyss Institute have created a small biological robot called the Ans robot from human tracheal cells that can move across surfaces and across damaged areas in experimental dishes. It was found to promote neuron growth.

The multicellular robots, which measure from the width of a human hair to the tip of a sharpened pencil, are built to self-assemble and have been shown to have significant healing effects on other cells. I did. This discovery is the starting point for the researchers' vision of using patient-derived biobots as new therapeutic tools to regenerate, cure, and treat diseases.

Human tracheal skin cells self-assemble into multicellular, moving organoids called Ansrobots. These images show an Ans robot with cilia (yellow) distributed in different patterns on its surface. The surface pattern of cilia correlates with different movement patterns, such as circular, wiggling, long curves, and straight lines.Credit: Gizem Gumuskaya, Tufts University

From Xenobots to Ansubots: A leap forward in biobotics

This advance builds on previous work in the labs of Michael Levin, the Vannevar Bush Professor of Biology in Tufts University's College of Arts and Sciences, and Josh Bongard of the University of Vermont, who created a multicellular biological robot from frog embryo cells called You can navigate hallways, collect materials, record information, heal injuries, and even replicate a few cycles yourself. At the time, researchers didn't know whether these abilities came from amphibian embryos or whether biobots could be constructed from cells from other organisms. seed.

In the current study, cutting edge science, Levin, along with doctoral student Gizem Gumskaya, were able to actually create bots from adult human cells without genetic modification, demonstrating several abilities beyond those observed in xenobots. I found that it is proven. The discovery answers broader questions raised by the lab: What are the rules that govern how cells assemble and work together in the body? We began to answer the broader question of whether it is possible to reconnect with the “body plan.'' Do you want to perform other functions according to your design?

Explore Ans robot's abilities

In this case, researchers gave human cells that had lived quietly in the windpipe for decades a chance to find a way to restart and create new structures and roles. “We wanted to find out what cells can do other than create default functions in the body,” said Gamskaya, who earned a degree in architecture before entering biology. “By reprogramming the interactions between cells, we can create new multicellular structures in the same way that we arrange stones and bricks to create various structural elements such as walls, archways, and columns. The researchers found that cells not only create new multicellular shapes, but also move in different ways across the surface of human neurons cultured in laboratory dishes, creating gaps created by scratching cell layers. discovered that new growth can be encouraged to fill the gap.

Although it is not yet clear how the Ansu robots encourage neuron growth, the researchers confirmed that neurons grow in areas where collections of Ansu robots called “superbots” gather.

“The cell assemblies we build in the lab can have functions beyond their functions in the body,” says John, director of the Allen Discovery Center at Tufts University and associate faculty member at the Wyss Institute. Levin said. “The existence of normal patient tracheal cells unaltered was very interesting and completely unexpected. DNA, can move on their own and promote neuronal growth throughout the injured area,” Levin said. “We are now investigating how the healing mechanisms work and looking at what else these structures can do.”

Gizem Gumskaya works in the laboratory to create the Ansu robot.Credit: Gizem Gumuskaya, Tufts University

Advantages of using human cells include the ability to build bots from a patient's own cells to perform therapeutic tasks without the risk of triggering an immune response or requiring immunosuppressive drugs. It lasts only a few weeks before it is broken down, so it is easily reabsorbed into the body after it has finished its work.

Furthermore, outside the body, Anthrobot can only survive in very specific laboratory conditions, with no risk of exposure or unintentional spread outside the laboratory. Similarly, they do not reproduce and there are no gene edits, additions, or deletions, so there is no risk of them evolving beyond existing protection measures.

How is Unrobot made?

Each Anthrobot begins as a single cell derived from an adult donor. The cells come from the surface of the trachea and are covered with hair-like projections that wave back and forth called cilia. Cilia help tracheal cells push out small particles that enter the airways of the lungs. We all experience the action of ciliated cells when we take the final step of expelling particles and excess fluid by coughing or clearing our throats. Previous work by other researchers showed that when cells are grown in the lab, they spontaneously form small multicellular spheres called organoids.

The researchers developed growth conditions on the organoids that encouraged cilia to point outward. Within a few days, they began moving around, propelled by cilia that act like oars. They looked at different shapes and types of movement – first. Key features observed in biorobotics platforms. Levin believes that adding other capabilities to the Ansu robot (for example, contributions from different cells) would allow the Ansu robot to react to its environment and move into the body to perform functions, or to build artificial tissues in the lab. He said that it could be designed to provide support. .

The team, with the help of Simon Garnier, New Jersey Institute of Technology, characterized the different types of Ans robots produced. They found that bots fall into several distinct categories of shape and movement, ranging in size from 30 to 500 micrometers (from the thickness of a human hair to the tip of a sharpened pencil), and that bots fall into several distinct categories of shape and movement, with nanotechnology and larger We observed that it fills an important niche among artificial devices. .

Some were spherical and completely covered with cilia, while others were more irregularly shaped or football-shaped, with more patchy cilia or only one side covered with cilia. They moved in straight lines, in tight circles, combined movements, or just sat and wiggled around. Those that were spherical and completely covered with cilia tended to become wigglers. Ans robots with unevenly distributed cilia tended to move forward for longer on straight or curved paths. Typically, they survived for about 45 to 60 days in laboratory conditions before being naturally biodegraded.

“The Ansu robot self-assembles in a laboratory dish,” said Gamskaya, who created the Ansu robot. “Unlike Xenobots, they do not require tweezers or scalpels to shape, and instead of embryonic cells, adult cells or even cells from elderly patients can be used. This is fully scalable and allows these bots to The ability to generate swarms in parallel is a good start for developing therapeutic tools.”

A collection of Anthrobots, or superbots (green), stimulates the growth of mechanically stripped neurons (red).Credit: Gizem Gumuskaya, Tufts University

Ansrobot: The future of healing and therapy

Levin and Gumuskaya plan to eventually create an Anthrobot with therapeutic uses, so they created a lab test to see how the robot heals wounds. The model involved growing a two-dimensional layer of human neurons, then simply scratching the layer with a thin metal rod, creating an open “wound” devoid of cells.

To ensure that the interstices were exposed to a high density of Ansu robots, they created “superbots,” clusters that naturally form when Ansu robots are confined to a small space. Superbots are primarily made up of Circlers and Wigglers, so they won't wander too far from the wound.

One might expect that genetic modification of Ansrobot cells would be required for Bots to promote neural growth, but surprisingly, unmodified Ansrobots caused significant regrowth and were not found on plates. formed a bridge of neurons of the same thickness as the remaining healthy cells. Neurons did not grow in the wound where the Ans robot was not present. At least in his simplified 2D world of a laboratory dish, the Anthrobot assembly facilitated efficient healing of living neural tissue.

According to the researchers, further development of the bot could help remove plaque build-up in the arteries of atherosclerosis patients, repair damage to spinal cord and retinal nerves, recognize bacteria and cancer cells, and target tissues with drugs. This could potentially lead to other uses, such as the delivery of Ansu robots could theoretically support tissue healing while also developing drugs that promote regeneration.

Cell blueprint and the possibility of regeneration

Gumuskaya explained that cells have an innate ability to self-assemble to form larger structures in certain fundamental ways. “Cells can form layers, fold, form spheres, sort and separate into types, fuse, and even migrate,” Gamskaya said. “Two important differences from inanimate bricks are that cells can communicate with each other to create these structures dynamically, and that each cell can be programmed for many functions such as movement, secretion of molecules, and detection of signals. We are thinking about how to combine these elements to create new biological body plans and functions that are different from those found in nature.”

Harnessing the inherently flexible rules of cell assembly will help scientists build bots, but it will be difficult to understand how nature's body's plans come together and how the genome and environment work together. It also helps you understand how to create and repair tissues, organs, and limbs. Treat them with regenerative therapy.

Reference: Gizem Gumuskaya, Pranjal Srivastava, Ben G. Cooper, Hannah Lesser, Ben Semegran, Simon Garnier, Michael Levin, “Motile Living Biobots Self-Construct from Adult Human Somatic Precursor Seed Cells,” November 2023. 30 days, cutting edge science.
DOI: 10.1002/advs.202303575