Researchers from Ben-Gurion University and Stanford have discovered raptoblasts – cells that respond to activin and break down, releasing deadly substances. A single cell killed up to 70 nearby cells in the lab, but medical applications are still a long way off.
An unusual immune mechanism, reminiscent of a bomb that explodes when it receives a signal, has been discovered in flatworms that are capable of regenerating their bodies. Researchers from Ben-Gurion University of the Negev and Stanford University have identified a previously unknown type of cell, called a raptoblast. When the cell receives a signal indicating infection or the presence of foreign tissue, it rapidly disintegrates and releases into its environment a mixture of substances capable of killing bacteria and nearby cells.
The study, published in the journal Cell, was led by Prof. Benjamin Rosenthal from the Faculty of Health Sciences and the Center for Regenerative Medicine at Ben-Gurion University, and Prof. Bo Wang from Stanford University.
The discovery was made during research on flatworms of the Planaria genus. These animals are best known for their extraordinary ability to regenerate: even after their bodies are cut into several pieces, each piece can in some cases develop into a complete worm. This ability makes them an important research system for understanding tissue regeneration, cell differentiation, and the reactions that occur when different tissues meet.
The cells that disappeared under the microscope
In the first observations, the researchers noticed cells that disappeared quickly, leaving behind a zone of dead cells. Further tests showed that this was not accidental cell death. The cells underwent a controlled process that was activated in response to activin – a signaling protein from the hormone family that is involved, among other things, in development, cell differentiation and the control of immune responses.
When the level of activin in the environment of the raptoblasts rose sharply, a rapid process of calcium release from internal stores and reorganization of the cytoskeleton began within the cell. Within about two minutes, the cell disintegrated and released toxic substances into its environment.
The response is not supposed to spread out of control. According to the researchers, a specific activin signal is required to activate the raptoblasts, and the substances they release lose their activity within about fifteen minutes. This creates a short-lived mechanism, activated in the area where danger has been detected.
In experiments in culture, the researchers found that a single raptoblast was capable of killing up to 70 cells around it. The mixture released damaged bacteria, flatworm cells, and mammalian cells, including human cancer cells tested in the laboratory.
"The speed and completeness of the cell destruction really surprised us," said Prof. Wang. He said that the cell's breakdown creates a wave of substances with a wide range of action, damaging what is in its immediate vicinity.
How the worm fights bacteria
The researchers examined the role of cells in the body by exposing the planarians to bacteria. In response to the presence of the bacteria, other cells in the area released activin. The signal activated the raptoroblasts, which broke down and released substances that damaged the membranes of the invading bacteria.
In another experiment, the researchers combined tissues from two different worms. The encounter between the tissues caused an accumulation of activin, mass activation of the hepatoblasts, and the formation of tissue damage. When the researchers removed the hepatoblasts through genetic modification, the destructive rejection response stopped.
The results suggest that the cells play a dual role: they may help protect against infections, but also participate in the recognition and destruction of foreign tissues.
The discovery expands the conventional picture of immune systems. It does not mean that a new type of exploding immune cell has been discovered in humans. Heptoblasts were identified and studied in planarians, and experiments with human cells were conducted only in culture to test the potency of the substances released from them.
Possible inspiration for future treatments
The ability of a single cell to rapidly release substances that attack a wide range of targets could inspire new ideas in cell engineering in the future. In principle, one could imagine engineered cells that would be activated only in a tumor or infection environment and attack abnormal cells or drug-resistant bacteria.
However, the road to such an application is long. Researchers still need to accurately identify all the substances released, understand how they work, examine how to prevent damage to healthy tissue, and develop safe control mechanisms. The fact that the substances also killed human cells in culture highlights the power of the mechanism, but also the risk involved in operating it without control.
"These findings reveal a new strategy that directly links a hormonal signal to an explosive immune response," said Prof. Rosenthal. He said the mechanism demonstrates the enormous diversity of ways that nature has evolved to deal with infections and foreign cells.
The study also included Choo Chai, Elia Sultan, Surdeep R. Sarkar, Lihan Jong, Danya Nance-Tsrafati, Orly Gershoni-Yahlum, Christine Jacobs-Wagner, and Hawa Racine Thiam. The study was supported, among others, by the European Research Council and the National Institutes of Health in the United States.
The article in the journal Cell
Short FAQ
Have exploding cells been found in humans?
No. Heptoblasts were identified in flatworms of the Planaria genus. The substances they released were also tested on mammalian and human cells in culture.
What causes cells to explode?
A sharp increase in activin triggers calcium release and reorganization of the cytoskeleton, and within about two minutes the cell disintegrates.
Can they be used against cancer?
Not yet. The damage to cancer cells has only been demonstrated in laboratory conditions. Much research is needed before a safe and controlled treatment can be developed.
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