This image shows how the CNF sheets can be used to capture EVs from multiple sites in the body. Image: Takao Yasui.
This image shows how the CNF sheets can be used to capture EVs from multiple sites in the body. Image: Takao Yasui.

A research team in Japan, led by Akira Yokoi at Nagoya University, has used cellulose nanofiber (CNF) sheets derived from wood cellulose to capture extracellular vesicles (EVs) from fluid samples and organs during surgery.

EVs are small structures produced by most cells, including cancerous cells, that play a crucial role in cell-to-cell communication. Extracting and analyzing EVs using this new technology has the potential to revolutionize early cancer diagnosis and open the door to personalized medicine. The researchers report their findings in a paper in Nature Communications.

Cancer is notorious for its poor prognosis; in many cases, it goes undetected until its advanced stages, leaving patients with limited treatment options. EVs could be used to detect cancer early while also providing vital information about its status and progression. This should assist physicians in monitoring and adjusting personalized cancer treatment plans. However, researchers have been limited in previous attempts to use EVs due to the lack of an effective strategy for isolating them.

Now, Yokoi and his colleagues have shown that CNF sheets made from wood cellulose can be used to extract EVs from fluid samples taken from ovarian cancer mice models. As the sheet has a porous nanostructure, it can absorb the EVs into its pores, which close upon drying. The researchers found that the sheets captured and preserved EVs from as little as 10µL of body fluids. In contrast, current standard methods, such as ultra-centrifugation, are more time-consuming and require much larger samples.

“We have developed the unique cellulose nanofiber by applying paper-making and solvent-displacement technology,” Yokoi said. “The cellulose nanofibers we use are a sustainable biomass material that comes mostly from wood cell walls. These sheets have attractive properties, such as being lightweight, high strength and, most importantly, easily biodegradable.”

Using the technique, the researchers successfully extracted and analyzed EVs, together with the microRNAs (miRNAs) contained within them, from the mice ovarian cancer models. As miRNAs differ between healthy and sick patients, they represent an ideal diagnostic marker for cancer.

The researchers also identified distinct sets of miRNAs in EVs collected from tumor surfaces, some of which decreased after tumor removal. Tracking the presence or absence of these miRNAs could be an easy way to analyze the effectiveness of treatment and tailor it according to tumor heterogeneity, meaning the way that cancer cells can have various characteristics and properties even in a single tumor.

The structure of the sheets is similar to that of medical gauze, so they can easily be attached and removed from organs during surgery, which the group demonstrated by testing the sheets on recently removed human organs. This test also led to a further discovery: that EVs on the surface of tumors displayed different miRNA profiles to EVs in tumor tissue.

"Organ surfaces were a previously unanalyzed EV subpopulation, which can now be subjected to biological assessments,” Yokoi said. “CNF paper enables the obtaining of EVs from multiple sites in the body. Then, by checking the molecular profiles of these EVs, we can monitor disease progression and tailor the selection of the best drug, contributing to personalized medicine."

Takahiro Ochiya, board member of the International Society for Extracellular Vesicles and president of the Japanese Society for Extracellular Vesicles, is enthusiastic about the potential of the sheets. “Exosome analysis using CNF sheets is an extremely novel method and is expected to have a variety of applications, including medical uses,” he said. “We expect this to be a major advance that will bring the knowledge of exosomes as medical research directly to patients.”

This research has broad implications, opening up the analysis of EVs during surgery, an unexplored area until now. Looking ahead, the research team is committed to advancing the medical applications of EV sheets for various diseases, improving diagnostic accuracy and helping to usher in the era of personalized medicine.

This story is adapted from material from Nagoya University, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.