A review of the regulatory mechanisms of extracellular vesicles-mediated intercellular communication

Abstract

Extracellular vesicles (EVs) are small, membrane-bound structures that are released from cells into the surrounding environment. These structures can be categorized as exosomes, microvesicles, or apoptotic vesicles, and they play an essential role in intercellular communication. These vesicles are attracting significant clinical interest as they offer the potential for drug delivery, disease diagnosis, and therapeutic intervention. To fully understand the regulation of intercellular communication through EVs, it is essential to investigate the underlying mechanisms. This review aims to provide a summary of the current knowledge on the intercellular communications involved in EV targeting, binding, and uptake, as well as the factors that influence these interactions. These factors include the properties of the EVs, the cellular environment, and the recipient cell. As the field of EV-related intercellular communication continues to expand and techniques improve, we can expect to uncover more information about this complex area, despite the current limitations in our knowledge.

Keywords: EV biogenesis; EV uptake; Exosome; Extracellular vesicle; Intercellular communication.

Fig. 1

The general introductions of EVs, including the compositions, the related physiological and pathological processes, and their clinical applications. EVs are lipid membranous vesicles. The communication based on EVs is related to their surface proteins and their cargoes including protein, lipid, and nucleic acids. EVs participate in diverse biological processes, such as cell motility, differentiation, proliferation, apoptosis, reprogramming, waste management, metastasis, and inflammation. The biological processes related to EVs are linked with their clinical potentials such as diagnosis based on their biomarker properties, drug delivery with their targeting properties, and targeting therapy using their communication properties

Fig. 2

The influence factors for the EV-cellular interaction. The influence factors include the surfaced characteristic molecules related to EV, progenitor cell and recipient cell; and the cellular environments of EVs. The characteristic surface molecules include protein, lipid, and glycan, while the cellular environments include temperature, pH and ECM

Fig. 3

The biogenesis, travelling, uptake and degradation of EVs. EVs biogenesis occurs in progenitor cells. Then various EVs are secreted by progenitor cells, such as exosomes, microvesicles and apoptotic bodies. Exosomes are secreted within the MVEs. Microvesicles are secreted by directly budding through the plasma membrane and apoptotic bodies are released via membrane blebbing. After traveling through the ECM, EVs may influence the cell phenotype by endocytosis, fusion, and signaling. Subsequently, EVs would go through their metabolism in the recipient cell via three possible pathways including degradation by the lysosome, being released outside of the recipient cell directly, and contents release into the cytoplasm of the recipient cell. (Abbreviation: ECM, extracellular matrix; MVE, multivesicular vesicle; ILVs, intraluminal vesicles)