Abstract

The majority of studies on extracellular vesicles (EVs) focused on samples isolated from liquid matrices, such as cell culture media and blood, due to their accessibility. However, recent research highlights the emerging roles of EVs derived from solid tissues, including the brain, muscles and tumors. Investigating EVs from the extracellular matrix of solid tissues offers insights into their microenvironment and potential biological influences on surrounding cells. This study presents a universal method for comparing EV-enriched samples from solid (human skeletal muscle biopsy) and liquid (human plasma) matrices, addressing technical challenges and minimizing biases in separation techniques. By employing optimized protocols and advanced analytical techniques, the study reveals differences in biomolecular composition, nanomechanical properties, particle yield, size distribution, and colloidal stability between human skeletal muscle and plasma EVs. Understanding these distinctions may contribute to the development of novel diagnostic assays for muscular pathologies and shed light on the roles of EVs in diverse tissue environments.