Cells “shed waste” to speed healing, aid recovery – study
Photo from WashU Medicine
When injured, cells deploy regulated responses to promote healing. These include a long-studied self-destruction process that clears away damaged cells and a more recently described phenomenon that helps older cells revert to a younger, regenerative state.
Now, a study in mice led by researchers at Washington University School of Medicine in St. Louis and Baylor College of Medicine has revealed a previously unknown purging process that appears to help injured cells revert to a stem cell–like state more quickly. The investigators named the response cathartocytosis, from Greek roots meaning “cellular cleansing.”
Published in Cell Reports, the study used a mouse model of stomach injury to shed light on how cells repair—or fail to repair damage caused by infection or inflammatory disease.
According to Jeffrey W. Brown, MD, PhD, assistant professor of medicine at WashU, cells responding to injury temporarily shed their mature machinery to become simpler, fast-dividing forms that repair tissue. Although first observed in the gastrointestinal tract, researchers believe the process likely occurs in other tissues as well.
The “vomiting” response
Brown compared the process to “vomiting” out waste, a shortcut that allows the cell to quickly declutter and focus on regrowing healthy tissue instead of relying on the slower, controlled breakdown of waste. But as with many shortcuts, there are risks. The researchers said that cathartocytosis is “fast but messy”, which may explain how injury responses go awry in cases of chronic damage. For instance, persistent cathartocytosis during infection signals chronic inflammation and recurring cell injury, conditions that create a breeding ground for cancer. The researchers add that the buildup of ejected cellular waste may also serve as a marker for identifying or tracking cancer.
The researchers identified cathartocytosis as part of a broader regenerative response called paligenosis, first described in 2018 by study senior author Jason C. Mills, MD, PhD. Mills, now at Baylor College of Medicine, began this work at WashU Medicine, where Brown was a postdoctoral researcher in his lab. In paligenosis, injured cells abandon their normal roles and reprogram into an immature, stem cell–like state capable of rapid division. At first, the team assumed this cellular decluttering occurred entirely within lysosomes, which digest waste slowly and in a contained manner.
But from the beginning, they noticed debris outside the cells. Initially dismissed as insignificant, the finding grew harder to ignore. Using a mouse model of stomach injury that reprogrammed mature cells into stem-like cells all at once, Brown observed that the “vomiting” response was widespread. This confirmed that cathartocytosis is not a random spill of waste but a standard feature of paligenosis. The team cautions, however, that while this process aids repair, it might also allow mature cells to take on cancer-like behavior in other contexts.
Cathartocytosis and cancer risk
While cathartocytosis may help injured cells move through paligenosis and regenerate tissue more quickly, it produces excess waste that can fuel inflammation, complicate chronic injuries, and raise cancer risk. Mills explained that in gastric cells, paligenosis, the reversion to a stem cell state for healing carries risks, particularly with the added inflammatory burden of cathartocytosis. He furthered that stomach cells are long-lived and tend to accumulate mutations over time. When many of these mutated cells revert to stem-like states during repair, especially in inflamed environments such as infection, the likelihood of harmful mutations expanding into cancer increases.
The team suspects cathartocytosis may contribute to persistent injury and inflammation in Helicobacter pylori infections, a major cause of ulcers and stomach cancer.
New strategies for diagnosis and treatment
The findings may also point to new strategies for detection and treatment. Brown and collaborator Koushik K. Das, MD, have developed an antibody that binds to waste products expelled during cathartocytosis, providing a way to identify when the process occurs at scale. Such detection could potentially serve as an early warning sign of precancerous changes. Brown added that a deeper understanding of
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