Plant Extracellular Vesicles: Current Landscape and Future Directions

Abstract

Plant cells secrete membrane-enclosed micrometer- and nanometer-sized vesicles that, similarly to the extracellular vesicles (EVs) released by mammalian or bacterial cells, carry a complex molecular cargo of proteins, nucleic acids, lipids, and primary and secondary metabolites. While it is technically complicated to isolate EVs from whole plants or their tissues, in vitro plant cell cultures provide excellent model systems for their study. Plant EVs have been isolated from the conditioned culture media of plant cell, pollen, hairy root, and protoplast cultures, and recent studies have gathered important structural and biological data that provide a framework to decipher their physiological roles and unveil previously unacknowledged links to their diverse biological functions. The primary function of plant EVs seems to be in the secretion that underlies cell growth and morphogenesis, cell wall composition, and cell–cell communication processes. Besides their physiological functions, plant EVs may participate in defence mechanisms against different plant pathogens, including fungi, viruses, and bacteria. Whereas edible and medicinal-plant-derived nanovesicles isolated from homogenised plant materials ex vivo are widely studied and exploited, today, plant EV research is still in its infancy. This review, for the first time, highlights the different in vitro sources that have been used to isolate plant EVs, together with the structural and biological studies that investigate the molecular cargo, and pinpoints the possible role of plant EVs as mediators in plant–pathogen interactions, which may contribute to opening up new scenarios for agricultural applications, biotechnology, and innovative strategies for plant disease management.

Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery

“…Several studies have demonstrated that plants are able to secrete EVs morphologically similar to those released by eukaryotic cells (for review see [ 62 , 63 ]). Transmission electron microscopy has revealed that plant-derived EVs have a spherical appearance with a bilayer membrane and an electron-dense core, similar to human EVs ( Figure 1 ).…”

Mucosal mRNA Vaccines. Merits and Perspectives

“…EVs from edible plants may represent an appealing alternative. EVs of plant cells closely resemble those of mammalians [36]. Plant EVs are constituted by a bilayer membrane, and it has been shown that they can be loaded with exogenous nucleic acids, including mRNA, regulatory small RNA, DNA plasmids [37][38][39].…”

mRNA Technology and Mucosal Immunization

“… Targeted Delivery: EVs can be engineered to express specific surface proteins that allow them to target specific cell types or tissues, thus enhancing the precision of vaccine delivery. Several methods have been developed to engineer EVs by modifying their surface with the purpose of targeting drug delivery [ 43 , 44 ]. For a systematic review, see the study by Raghav and colleagues [ 45 ].…”

“…Since upscaling cultures of human cells to produce EVs is technically demanding and requires complex purification stages as well as difficult biosafety controls, alternative resources are being explored. EVs from edible plants closely resemble EVs of mammalian tissues [ 44 ]. They are constituted by a bilayer membrane and can be loaded with exogenous nucleic acids, including mRNA, regulatory small RNA, and DNA plasmids [ 46 , 84 , 85 ].…”