Introduction of cellulose nanofiber-based EV sheets for novel exosome analyses

Abstract

My research group recently developed a novel method for isolating extracellular vesicles (EVs) using cellulose nanofiber (CNF) sheets, termed as EV sheets, which are designed with tunable pore sizes. EVs, including exosomes, play a crucial role in cellular communication and are key targets of disease mechanisms. EV sheets capture intact EVs from minimal volumes of biofluid, such as the surfaces of organs, and store them under dry conditions until analysis. These EV sheets addressed the current limitations of EV research. CNF Sheets provide a breakthrough by effectively isolating and preserving EVs from as little as 10 µL of biofluid. In ovarian cancer models and patient samples, EV sheets revealed spatial heterogeneity in the EV profiles and identified unique miRNA signatures based on their location. This technique detects cancer-associated miRNAs at an early stage before visible symptoms such as ascites develop. Importantly, the miRNA profiles obtained from tumor surfaces differed from those obtained from the surrounding fluids, providing a better understanding of tumor-derived EVs. The EV sheet isolation method has a high EV recovery efficiency and compatibility with small RNA sequencing, demonstrating its potential to advance cancer diagnosis, staging, and treatment planning. EV sheets also offer advantages in EV preservation and transport, making them practical for clinical and research applications. In addition, this method is promising for elucidating EV biology, particularly its role in cancer progression and intercellular communication. Future studies will aim to refine this method for wider clinical use and maximize its potential.