Unique Cellular Signal Directs Cells to Gobble Up Toxic Waste; Could Serve as New Weapon to Fight Disease

White blood cells have a lot of work to do. They are our body’s main defense against foreign invaders—and are quite adept at it. Tasked with cleanup duty, they target and destroy cells that have been infected with bacteria, viruses or other harmful, disease-causing pathogens.

But as good as they are at their job—they aren’t perfect. Sometimes they need a little help. This is where modern medicine steps in to help the body fight disease.

A healthy cell (green) that has recognized and engulfed dying cells (purple) is shown. [Credit: Toru Komatsu/University of Tokyo]

A healthy cell (green) that has recognized and engulfed dying cells (purple) is shown. [Credit: Toru Komatsu/University of Tokyo]

But what if we could reprogram human cells, and supercharge them—so that they are then able to do the job that as of right now, only the most advanced drugs could accomplish. This is the hope of scientists from Johns Hopkins University, who today report that they are on the path towards doing just that.

Published online in the journal Science Signaling, Dr. Takanari Inoue and his team at Hopkins—along with his collaborators at the University of Tokyo—have together pioneered an innovative way to transform cells not normally involved in fighting disease into a new, cellular line of defense.

This discovery could potentially alter how our bodies combat some of humankind’s most relentless diseases—including pathogens that are skilled at evading white blood cells, or even cancer cells that can grow out of control and lead to dangerous tumors.

As Inoue explained in today’s news release:

“Our goal is to build artificial cells reprogramed to eat up dangerous junk in the body, which could be anything from bacteria to…the body’s own rogue cancer cells. By figuring out how to get normally inert cells to recognize and engulf dying cells, we’ve taken an important first step in that direction.”

A class of white blood cells called macrophages normally target and destroy dangerous cellular ‘junk’ via a process called phagocytosis. Phagocytosis is a fundamental but complex cellular process, so Inoue and his team broke it down step by step. In this way, they hoped to find out the bare minimum process needed, in order to give cells the power of phagocytosis.

The team started with a type of laboratory grown cell called HeLa. The first step was to tweak HeLa cells so that they could target and attach to dying cells. The second step was to destroy those dying cells.

The first step was accomplished simply by modifying a particular protein that sits on the surface of HeLa cells so that damaged or dying cells would be attracted to them. By making this modification, up to six dying cells locked onto each HeLa cell.

Next, the team switched on a gene in the HeLa called Rac. Previous research by other teams had found that turning on Rac causes a cell to engulf whatever is attached to it. In this case, activating Rac spurred the HeLa cells to swallow up the dying cells already attached to its surface. In effect, they had changed the cells’ job description—allowing them to mimic the phagocytosis process normally reserved for certain white blood cells.

As Inoue elaborated:

“We’ve shown it’s possible to endow ordinary cells with the power to do something unique: take on the role of a specialized macrophage.”

These results, while encouraging, are still preliminary. For example, even though the HeLa cells engulfed the dying cells, they likely weren’t destroyed. This next step in phagocytosis will be critical if the researchers are to further develop the idea of modifying the body’s own cells to combat disease.

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