Studying a Cell’s 'Messages in a Bottle' to Unlock Clues to Disease
Cells have a variety of ways of communicating with one another, cytokines and neurotransmitters being two such methods.
But a growing body of science now points to another key mechanism for cells to send signals over long distances. All cells produce extracellular vesicles (EVs), tiny membrane-bound particles that carry important genetic information, proteins and lipids that reflect the cell of origin. These EVs float through the bloodstream, urine and saliva, serving as tiny “messages in a bottle.”
Initially considered mere cellular “trash bags,” EVs are now seen as more complex because they contain protected genetic material and other signaling molecules from their parent cells.
“Inside these EVs are contents that can be very specific to the cell or tissue they came from,” says Theresa Wilson, VP of Precision Medicine within Early Clinical Development.
Scientists are hoping this encapsulated material within EVs can be used to diagnose disease. For example, studies have shown that EV concentration is elevated in cancer patients.
“We hope EVs can be a source of biomarkers for us to get tissue-level information without having to do an invasive biopsy,” says Wilson. Researchers are also exploring EVs as drug delivery vehicles and for their therapeutic properties. “We're starting to learn significantly more about EVs than we knew even a few years ago. This is a rapidly growing area of science,” she says.
Exponential insights and evolving applications
Scientists are now exploring ways to use antibodies to detect tissue-specific EVs found in the blood and other bodily fluid samples. This enables researchers to isolate EVs by organ type.
“Theoretically, we should be able to pull down EVs for each of the tissue types in the body providing we can identify a tissue specific marker,” says Wilson.
Traditionally, in diagnosing diseases like NASH (non-alcoholic steatohepatitis), in which the liver is damaged by inflammation due to a buildup of fats, clinicians would have to conduct an invasive liver biopsy to obtain a tissue sample. However, scientists are now exploring ways to study liver-derived EVs from a simple blood sample that could provide an understanding of the disease.
“We normally don’t have insights into what’s going on at the tissue level without taking a biopsy,” says Wilson. “We currently have to make assumptions on what’s going on in the liver from biomarker measurements from blood. But with liver-specific EVs, we have the opportunity to gain insights about what’s going on in the liver in real time.”
Similarly, if scientists wanted to study markers for inflammatory bowel disease, for example, they could isolate gut EVs from blood samples.
“In the future we hope to be able to understand what’s going on in the gut in a clinical trial without having to take a biopsy,” says Wilson.
Scientists are also studying EVs secreted by immune cells to better understand the inflammation status of patients, says Jorge Schettini, a Principal Scientist at Pfizer’s Cambridge, MA research site. Schettini and colleagues are working on a pilot project to show that several key immune cell proteins that act as long-distance regulators are expressed on the surface of EVs.
We hope EVs can be a source of biomarkers for us to get tissue-level information without having to do an invasive biopsy.
EVs may also provide important clues on how medicines are impacting the body’s organs. Sometimes medicines may cause the gut or liver to produce more or less of certain enzymes, but there are limited non-invasive tools to measure these effects. By studying gut and liver-derived EVs, scientists may be able to tell what’s happening in those organs, saving time in the drug development process. Therefore, Pfizer scientists in Medicine Design and Precision Medicine are currently collaborating with Flinders University (Adelaide, Australia) on a project that shows how gut- and liver-specific plasma EVs can provide insights into how a drug affects the two tissues over time.
“Typically, these drug interactions are assessed in clinical trials through a dosing process in study subjects,” says David Rodrigues, a Senior Scientific Director at Pfizer. “We can minimize such tests by measuring the tissue-derived plasma EVs themselves for various enzyme activities.”
These tiny packets of cellular information offer promise in targeting specific tissue types, including cancer cells. Scientists are studying ways to package medicines inside EVs to deliver otherwise toxic materials to tumors. And because EVs are naturally made in the body, they have the ability to target tissues and evade the immune system.
“EVs carrying potent anti-tumor drugs are like undercover agents,” says Han. “They may reach a tumor without getting eliminated by our bodies and possibly enhance drug delivery to tumors with less toxicity.”
“It’s sort of a natural nanoparticle,” says Wilson.
As scientists uncover more and more about these cellular communication vehicles, the potential for therapeutic and diagnostic benefits expands. “It’s an exciting and evolving area of science right now. That’s why we’re exploring collaborations to help drive advances,” says Wilson.