In the Nagoya University team’s kidney-cell experiment, the share of tiny blood-and-urine particles carrying one inflammation-linked RNA rose from about one in 10 to about four in 10 after the cells received inflammatory signals. That change points to a possible way to find not only signs of chronic inflammation, but also clues about the tissue involved.
Chronic inflammation can continue for months or years, even when there is no clear threat to the body. Over time, it can damage tissue and contribute to conditions including cancer, brain disorders, autoimmune diseases and heart disease. Existing blood tests, such as those that measure C-reactive protein, can detect inflammation, but they often cannot show where it is happening. “These biomarkers can detect inflammation, but it is difficult to identify where it occurs,” said Taiga Ajiri, an assistant professor at Nagoya University’s Yasui Lab.
Ajiri and colleagues looked to extracellular vesicles, or EVs: tiny, membrane-wrapped particles released by cells and carried through fluids such as blood and urine. An EV can hold clues on both sides of its membrane. Surface proteins may point to the tissue it came from, while microRNAs inside can reflect the state of its original cell. Usually, researchers have to break open vesicles to study those inner molecules, mixing material from many particles and losing the link between a vesicle’s contents and its surface.
The new method aims to keep that package intact. The team used meshlike sheets made from wood-derived cellulose nanofibers to capture EVs. They paired the vesicles with lipid nanoparticles carrying molecular beacons, probes that glow when they bind to selected microRNAs. Drying on the sheets brings the membranes close enough to fuse, allowing the probes to enter an EV without breaking it open.
To test the approach, the researchers created a laboratory model of chronic active antibody-mediated rejection, a complication of kidney transplants, by exposing human kidney cells to inflammatory signals. They found 71 microRNAs whose levels changed in EVs released by the cells. The team focused on miR-1246 and the kidney-associated surface protein DPYS, combining a possible inflammation signal with a clue about tissue origin.
After allowing for detection efficiency, the researchers estimated that miR-1246 was present in about 10% of EVs from unstimulated kidney cells and about 40% after inflammatory stimulation. A standard qPCR test, which measures genetic material in a sample, did not find a statistically significant difference using equivalent sample amounts. The result suggests that reading individual vesicles may reveal changes that are harder to see when many particles are measured together.
The team also analyzed urine from kidney transplant patients with the rejection complication, people with immune diseases not mainly involving the kidney, and healthy volunteers. The reported source does not provide the results of that comparison, so the method’s performance in patients remains unclear. Published in Cell Reports Physical Science, the work is an early step toward noninvasive tests that could detect inflammation and help identify affected tissues. Further studies will need to show whether the approach works reliably in people and across different diseases.