Madrid – In a breakthrough that redefines our understanding of cellular cleanup, researchers have, for the first time, directly observed healthy cells actively dismantling and consuming their damaged counterparts. The international study, conducted by teams in Spain and Australia, offers unprecedented insight into the process of phagocytosis and its critical role in preventing inflammation-a key factor in diseases ranging from arthritis to cancer. Published this week in Science Advances, the findings reveal a surprisingly active role for neighboring cells in preparing defective cells for disposal, potentially opening new avenues for therapeutic intervention.
Natural Process Boosts Removal of Faulty Cells, Study Finds
MADRID, Dec. 22 — Researchers have captured the first-ever footage of a natural process where healthy cells actively break down and consume damaged or dying cells, a finding that could have implications for understanding and treating inflammatory diseases.
The study, conducted by scientists at the Institute of Molecular Biology of Barcelona (IBMB-CSIC) and La Trobe University in Australia, visually demonstrates how cells in living tissue surround defective cells, dismantle them into smaller components, and then engulf and eliminate them. Understanding how the body clears out these faulty cells is crucial, as their accumulation can trigger inflammation in organs like the lungs and intestines.
Previous research on cell death, known as apoptosis, suggested that damaged cells self-destruct by breaking down into fragments. However, this new work reveals a more active role for neighboring healthy cells. “We’ve seen that this isn’t necessarily the case; it’s the neighboring cells that break them down before ingesting them,” explained Esteban Hoijman, a researcher at IBMB-CSIC and the Bellvitge Biomedical Research Institute (IDIBELL).
The findings, published in the journal Science Advances, were observed in live tissue samples from zebrafish and mice. The research provides unprecedented detail about the body’s natural mechanisms for removing cells that are no longer functioning properly.
Millions of cells die each day, either through natural turnover or because they are defective. This controlled process, apoptosis, ensures that these dead cells are recognized and cleared away by other cells through a process called phagocytosis. During phagocytosis, cells surround, engulf, and digest cellular debris. When this clearance system fails, the buildup of dead cells can lead to various inflammatory conditions.
One challenge in phagocytosis is the size of the cells involved – both the engulfing and the engulfed cells are often similar in dimension. To overcome this, the study found that cells must be broken down into smaller pieces before they can be effectively ingested.
“Until now, it was thought that the defective cell itself would break down into fragments during apoptosis, a process of self-destruction,” Hoijman said. “However, we have observed that neighboring cells ‘chew’ the cells they are about to ingest, breaking them into smaller parts to facilitate ingestion. This process is similar to how we chew food in our mouths, but at a microscopic level.”
The cells performing the phagocytosis extend surface projections that exert force on the target cells, effectively breaking them apart. These projections are used both for breaking down the cells and for engulfing the resulting fragments, functioning almost like a mouth, researchers noted.
The study’s findings offer a deeper understanding of apoptosis and phagocytosis, essential processes for both normal bodily function and embryonic development. Researchers also point out that many diseases linked to inflammation in the intestines, lungs, and joints – such as colitis, respiratory allergies, and arthritis – involve a failure to adequately remove accumulating cells. Furthermore, disruptions in apoptotic processes can contribute to diseases like cancer and neurodegeneration, the researchers explained.
“This discovery helps us better understand how the body eliminates cells that are no longer useful, opens the door to new research to improve phagocytosis, and could potentially lead to the development of drugs that enhance this capability,” Hoijman concluded. The research could pave the way for new therapeutic strategies targeting inflammatory diseases and cellular dysfunction.
