In a groundbreaking study, researchers from Washington University School of Medicine in St. Louis and Baylor College of Medicine have uncovered a novel cellular process that could revolutionize our understanding of cell healing and cancer development. The study, conducted on mice and published in the journal Cell Reports, reveals a previously unknown mechanism by which injured cells purge themselves of waste to revert more rapidly to a stem cell-like state. This process, termed cathartocytosis, could have significant implications for regenerative medicine and oncology.
The discovery was made using a mouse model of stomach injury, shedding light on how cells respond to damage from infections or inflammatory diseases. According to Dr. Jeffrey W. Brown, the study’s first author and an assistant professor of medicine at WashU Medicine, “After an injury, the cell’s job is to repair that injury. But the cell’s mature cellular machinery for doing its normal job gets in the way.” He likened cathartocytosis to a cellular “vomiting” of waste, allowing cells to quickly become primitive, proliferative entities capable of repairing tissue.
The Mechanics of Cathartocytosis
The study builds on previous research into paligenosis, a process first described in 2018 by Dr. Jason C. Mills, now at Baylor College of Medicine. Paligenosis involves the reprogramming of injured cells to a stem cell-like state, enabling them to divide rapidly and heal tissue. Initially, researchers believed this decluttering occurred entirely within lysosomes, cellular compartments responsible for digesting waste. However, the observation of debris outside cells led to the identification of cathartocytosis as a deliberate, standard cellular response.
Brown’s team discovered that cathartocytosis is not merely an accidental spill but a crucial component of paligenosis. This cellular purging could potentially occur in other contexts, such as when mature cells begin to mimic cancerous behavior. The rapid but messy nature of cathartocytosis may illuminate how injury responses can become problematic, particularly in chronic injury settings.
Implications for Cancer and Chronic Inflammation
While cathartocytosis may accelerate tissue regeneration, it also poses risks. The process generates additional waste products, potentially fueling chronic inflammation and increasing cancer risk. Dr. Mills highlighted the dangers, stating, “In these gastric cells, paligenosis — reversion to a stem cell state for healing — is a risky process, especially now that we’ve identified the potentially inflammatory downsizing of cathartocytosis within it.”
The researchers suggest that cathartocytosis might play a role in perpetuating injury and inflammation in conditions like Helicobacter pylori infections, which are known to increase stomach cancer risk. The findings could pave the way for new treatment strategies for stomach and other gastrointestinal cancers.
Future Research and Potential Applications
Looking ahead, the research team, including Dr. Koushik K. Das, has developed an antibody that binds to the waste products of cathartocytosis. This innovation could allow for the detection of precancerous states, enabling early intervention and treatment. “If we have a better understanding of this process, we could develop ways to help encourage the healing response and perhaps, in the context of chronic injury, block the damaged cells undergoing chronic cathartocytosis from contributing to cancer formation,” Brown explained.
The study was supported by grants from the National Institutes of Health, the Department of Defense, the American Gastroenterological Association, and a Philip and Sima Needleman Student Fellowship in Regenerative Medicine. The authors emphasize that the content is their responsibility and does not necessarily represent the NIH’s official views.
As research continues, cathartocytosis could become a key focus in the quest to balance rapid tissue repair with the prevention of chronic inflammation and cancer, offering new hope for regenerative medicine and cancer therapy.
