Challenges and directions in studying cell–cell communication by extracellular vesicles

Niel, Guillaume van; Carter, David R. F.; Clayton, Aled; Lambert, D; Raposo, Graça; Vader, Pieter

doi:10.1038/s41580-022-00460-3

Cited by 546 publications

(478 citation statements)

References 101 publications

(127 reference statements)

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“…EVs conform to a highly complex population demonstrated by high heterogeneity in size, biogenesis, origin, content, mechanism of action, and biological function. Indeed, their biogenesis, uptake by target cells and cargo delivery processes (endocytosis, trafficking to endo/lysosomes, membrane fusion, cargo release, and phenotypic changes in the recipient cell) are still unclear (please refer to the comprehensive review for detailed EV basic biology [ 13 ]). Mass spectrometry-based proteomics have shown that cargo selection mechanisms are highly regulated by post-translational modifications [ 14 ].…”

Section: Extracellular Vesicles: Current State and Emerging Conceptsmentioning

confidence: 99%

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

Suades

Greco

Padró

et al. 2022

Cells

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Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality all over the world. Extracellular vesicles (EVs), small lipid-bilayer membrane vesicles released by most cellular types, exert pivotal and multifaceted roles in physiology and disease. Emerging evidence emphasizes the importance of EVs in intercellular communication processes with key effects on cell survival, endothelial homeostasis, inflammation, neoangiogenesis, and thrombosis. This review focuses on EVs as effective signaling molecules able to both derail vascular homeostasis and induce vascular dysfunction, inflammation, plaque progression, and thrombus formation as well as drive anti-inflammation, vascular repair, and atheroprotection. We provide a comprehensive and updated summary of the role of EVs in the development or regression of atherosclerotic lesions, highlighting the link between thrombosis and inflammation. Importantly, we also critically describe their potential clinical use as disease biomarkers or therapeutic agents in atherothrombosis.

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Section: Extracellular Vesicles: Current State and Emerging Conceptsmentioning

confidence: 99%

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

Suades

Greco

Padró

et al. 2022

Cells

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“…These vesicles clearly have potential and may open new possibilities for precise medicine. However, many aspects of RBCEVs are still unclear such as how RBCEVs interact with other tissues and organs [ 120 ]; there are still challenges for their clinical translation. Therefore, research based on different disciplines is needed to realize the full potential of RBCEVs.…”

Section: Discussionmentioning

confidence: 99%

Roles and Applications of Red Blood Cell-Derived Extracellular Vesicles in Health and Diseases

Yang

Huang

Zhang

et al. 2022

IJMS

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Red blood cell-derived extracellular vesicles (RBCEVs) are vesicles naturally produced by red blood cells and play multiple roles such as acting as cell-to-cell communication messengers in both normal physiological and diseased states. RBCEVs are highly promising delivery vehicles for therapeutic agents such as biomolecules and nucleic acids as they are easy to source, safe, and versatile. RBCEVs autonomously target the liver and pass the blood–brain barrier into the brain, which is highly valuable for the treatment of liver and brain diseases. RBCEVs can be modified by various functional units, including various functional molecules and nanoparticles, to improve their active targeting capabilities for tumors or other sites. Moreover, the RBCEV level is significantly shifted in many diseased states; hence, they can also serve as important biomarkers for disease diagnoses. It is clear that RBCEVs have considerable potential in multiple medical applications. In this review, we briefly introduce the biological roles of RBCEVs, presented interesting advances in RBCEV applications, and discuss several challenges that need to be addressed for their clinical translation.

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“…We confirmed that they were all present as full-length in BDEVs, and therefore, have at least the potential to be translated in the recipient cells. However, studying the biological relevance of the mRNA content (and other RNA cargoes) in EVs and proving their functionality in the recipient cells is very challenging [ 68 , 69 ]. It has been shown in EVs of human glioblastoma stem cells that the number of mRNAs is substantially low, as it was estimated to be 1 copy in 1,000 EVs for the most abundant mRNA, and for others less than 1 copy every 10,000–100,000, or even 1 copy in a million EVs for some RNA species.…”

Section: Discussionmentioning

confidence: 99%

Multiplexed mRNA analysis of brain-derived extracellular vesicles upon experimental stroke in mice reveals increased mRNA content with potential relevance to inflammation and recovery processes

Bub

Brenna

Alawi

et al. 2022

Cell. Mol. Life Sci.

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Extracellular vesicles (EVs) are lipid bilayer-enclosed structures that represent newly discovered means for cell-to-cell communication as well as promising disease biomarkers and therapeutic tools. Apart from proteins, lipids, and metabolites, EVs can deliver genetic information such as mRNA, eliciting a response in the recipient cells. In the present study, we have analyzed the mRNA content of brain-derived EVs (BDEVs) isolated 72 h after experimental stroke in mice and compared them to controls (shams) using nCounter® Nanostring panels, with or without prior RNA isolation. We found that both panels show similar results when comparing upregulated mRNAs in stroke. Notably, the highest upregulated mRNAs were related to processes of stress and immune system responses, but also to anatomical structure development, cell differentiation, and extracellular matrix organization, thus indicating that regenerative mechanisms already take place at this time-point. The five top overrepresented mRNAs in stroke mice were confirmed by RT-qPCR and, interestingly, found to be full-length. We could reveal that the majority of the mRNA cargo in BDEVs was of microglial origin and predominantly present in small BDEVs (≤ 200 nm in diameter). However, the EV population with the highest increase in the total BDEVs pool at 72 h after stroke was of oligodendrocytic origin. Our study shows that nCounter® panels are a good tool to study mRNA content in tissue-derived EVs as they can be carried out even without previous mRNA isolation, and that the mRNA cargo of BDEVs indicates a possible participation in inflammatory but also recovery processes after stroke.

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Challenges and directions in studying cell–cell communication by extracellular vesicles

Cited by 546 publications

References 101 publications

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

Roles and Applications of Red Blood Cell-Derived Extracellular Vesicles in Health and Diseases

Multiplexed mRNA analysis of brain-derived extracellular vesicles upon experimental stroke in mice reveals increased mRNA content with potential relevance to inflammation and recovery processes

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