When injured, cells have well-regulated responses to promote healing.These include a long-studied self-destruction process that cleans up dead and damaged cells, and a more recently identified phenomenon that helps older cells revert to a younger state to grow back healthy tissue.
Now, a new study in mice from Washington University school of Medicine in St. louis and the Baylor College of Medicine reveals a previously unknown cellular purging process. This process helps injured cells revert to a stem cell-like state more rapidly. researchers dubbed this newly discovered response cathartocytosis, from Greek roots meaning “cellular cleansing.”
Published in Cell Reports, the study used a mouse model of stomach injury to provide new insights into how cells heal—or fail to heal—from damage caused by infection or inflammatory disease.
“After an injury, a cell’s job is to repair it. but the cell’s mature machinery gets in the way,” said first author Jeffrey W. Brown, MD, PhD, an assistant professor of medicine at WashU Medicine. “This cellular cleanse is a rapid way to get rid of that machinery, allowing it to rapidly become a small, primitive cell capable of proliferating and repairing the injury. We identified this process in the GI tract, but suspect it’s relevant in other tissues too.”
Brown likened the process to a cell “vomiting” waste, adding a shortcut to declutter and focus on regrowing healthy tissues faster than gradual degradation would allow.
This shortcut has potential downsides. Cathartocytosis is fast but messy, potentially explaining how injury responses can go wrong, especially with chronic injury. Ongoing cathartocytosis from an infection signals chronic inflammation and recurring cell damage—a breeding ground for cancer. The ejected cellular waste may even be a way to identify or track cancer, the researchers suggest.
A Novel cellular Process
The researchers identified cathartocytosis within paligenosis, an crucial regenerative injury response first described in 2018 by senior author Jason C. Mills, MD, PhD. Mills is now at the Baylor College of Medicine, having previously been a faculty member at WashU medicine, where Brown was a postdoctoral researcher.
In paligenosis, injured cells shift roles and reprogram to an immature state, behaving like rapidly dividing stem cells.Initially, researchers believed this decluttering happened entirely within lysosomes, where waste is slowly digested.
Though, they noticed debris outside the cells. Brown suspected something deliberate was happening as the waste accumulated. Using a mouse stomach injury model, he showed the “vomiting” response happened simultaneously in all stomach cells, proving it was a standard cellular behavior, not an accident.
Although discovered during paligenosis, cells could potentially use cathartocytosis in other situations, like allowing mature cells to act like cancer cells.
The Downside to Downsizing
While cathartocytosis may help cells regenerate tissue rapidly through paligenosis, it also creates additional waste that could fuel inflammation, hindering chronic injury resolution and increasing cancer risk.
“In these gastric cells, paligenosis—reversion to a stem cell state for healing—is risky, especially now that we’ve identified the potentially inflammatory downsizing of cathartocytosis within it,” Mills said. “Aging cells acquire mutations. If many older, mutated cells revert to stem cell states to repair an injury—and injuries frequently enough fuel inflammation—there’s an increased risk of acquiring, perpetuating, and expanding harmful mutations that lead to cancer as those stem cells multiply.”
More research is needed, but the authors suspect cathartocytosis could play a role in perpetuating injury and inflammation in Helicobacter pylori infections, which damage the stomach and increase stomach cancer risk.
The findings could also lead to new treatment strategies for stomach and other GI cancers. Brown and WashU Medicine collaborator Koushik K.Das, MD, have developed an antibody that binds to cellular waste ejected during cathartocytosis, allowing detection of this process. This could serve as a marker for precancerous states, enabling early detection and treatment.
“If we better understand this process, we could develop ways to encourage healing and potentially block damaged cells undergoing chronic cathartocytosis from contributing to cancer formation,” Brown said.
This work was supported by the National Institutes of health (NIH), grants K08DK132496, R21AI156236, P30DK052574, P30DK056338, R01DK105129, R01CA239645, F31DK136205, K99GM159354 and F31CA236506; the Department of Defense, grant W81XWH-20-1-0630; the American Gastroenterological Association, grants AGA2021-5101 and AGA2024-13-01; and a philip and Sima Needleman Student Fellowship in Regenerative Medicine. The content is solely the responsibility of the authors and dose not necessarily represent the official views of the NIH.
