Stanford Scientists Discover an Immune Cell That Kills by Exploding

Stanford scientists have discovered a new type of immune cell in planarian flatworms that destroys surrounding cells by exploding—vanishing completely within minutes and leaving no trace behind. The cells, which the research team named "ruptoblasts," undergo a form of cell death called "ruptosis" when triggered by a specific hormone.

Planarian flatworms are known for their remarkable ability to survive dismemberment and regenerate whole organisms from individual segments. Understanding how their immune systems have persisted for hundreds of millions of years, the researchers say, could offer insights relevant to modern medicine.

"We never expected that a cell could just explode like a bomb and kill the cells surrounding it," said Bo Wang, senior author of the paper published in Cell.

The discovery began when postdoctoral researcher Chew Chai, the paper's lead author, was investigating whether flatworms could distinguish their own tissues from those of another individual. She fused longitudinally sliced flatworms with separate worms and observed that, despite their regenerative abilities, the worms rejected foreign tissue in a manner similar to organ transplant rejection in humans. What followed was unlike any known immune response.

"It's this huge inflammatory response. Like there's a fire and an alarm goes off, and the cells just blow up," Chai said.

Chai had also observed a spike in levels of the hormone activin during tissue rejection, along with subsequent chronic inflammation. Injecting otherwise healthy flatworms with activin triggered a similar response. Using live-cell microscopy and flow cytometry, Chai stained and sorted individual cells to isolate those responding to activin. A subset burst open, released contents that killed surrounding cells, and disappeared within five minutes.

What makes ruptosis distinct is its speed. "Some mammalian cells and bacteria may also do an explosive sort of cell death, but the timescale is really long. They are exploding, but it's more like pores that slowly leak things out over the course of several hours," Chai said. "Ruptosis happens within seconds to minutes."

In lab tests, ruptoblasts killed E. coli bacteria, human kidney cells, and mouse blood cells. Critically, the destruction remained localized—no chain reaction, no lingering toxicity—a characteristic Wang says holds promise for targeted treatments of bacterial infections or tumors.

Ruptoblasts are also structurally distinct from common immune cells like T-cells or neutrophils in that they are glandular cells, not blood-derived hematopoietic cells. Chai found these cells only in basal bilaterians like flatworms, suggesting early evolutionary origins. She speculates they may have been filtered out of vertebrate immune systems because vertebrates, unlike stem-cell-rich flatworms, lack the repair capacity to recover from ruptosis.

"It demonstrates there's lots of different immune mechanisms out there," Wang said. "There's all these animals that live in an environment where there's lots of bacteria, lots of viruses, and we know so little about their immune mechanisms."