Unveiling the Lipid Landscape of Extracellular Vesicles: From Biogenesis to Therapeutic Potential

Extracellular vesicles (EVs) are lipid-bound particles produced and released by various cells, classified into three subgroups: exosomes, ectosomes, and apoptotic bodies. Initially believed to function solely in cellular debris degradation, EVs were later found to carry a diverse array of biomolecules, including proteins (e.g., Rab GTPases, annexins, flotillin, ALG-2-interacting protein X, and tumor susceptibility gene 101 protein) and lipids (e.g., cholesterol, sphingolipids, ceramide, and glycerophospholipids). This discovery significantly expanded their recognized role in intercellular communication and biological processes.

Recent research has further highlighted the importance of EV lipids in regulating biogenesis, metabolism, and distribution. Despite increasing interest in lipidomic research, it remains significantly underexplored compared to proteomic analyses. Given their crucial role in EV formation and interactions, variations in lipid profiles have been linked to different cell origins and pathological conditions such as Alzheimer’s disease and cancer. Their involvement in disease pathogenesis, inflammation, and immunity underscores the necessity of characterizing EV lipid composition.

"Lipid roles in different stages of EV biogenesis" Created using BioRender published by the author in https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1198044/full

Lipids play diverse functional roles in the body, influencing various stages of EV biogenesis while altering their metabolism and distribution. Notably, variations in lipid composition have been observed in EV membranes derived from different cell types. Studies have also established links between lipid enrichment in EVs and factors such as head group charge, fatty acid tail length, and saturation. These findings highlight the need to consider multiple exosome properties for accurate data interpretation. Furthermore, as lipids are essential in EV generation and release from parent cells, understanding their structural impact on cell membranes could drive advancements in EV biogenesis. Such insights may prove particularly valuable for applications requiring high-throughput EV production.

Enhancing lipidomic analysis techniques could unlock new possibilities for manipulating EV lipids, potentially revolutionizing disease intervention strategies. By developing comprehensive lipidomic maps and refining EV engineering, researchers can pave the way for novel biomarkers and therapeutic approaches, particularly for conditions that demand scalable EV production.

The diagnostic and therapeutic potential of EVs. Created by the author in BioRender.

Written by Samaneh Ghadami, 4th year PhD student in the NBI Lab

April 25, 2025