Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials

Vlassov, Alexander V.; Magdaleno, Susan; Setterquist, Robert A.; Conrad, Rick

doi:10.1016/j.bbagen.2012.03.017

Cited by 1,687 publications

(1,527 citation statements)

References 68 publications

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“…The pooled vesicles had an average density of 1.07 g ml −1 (Figure 1(c)). These data are in agreement with values reported on exosome densities in other cell types [36]. Combined, the data indicate that the embryonic kidney-derived exosomal fraction consists mostly of a homogenous population of vesicles with features of exosomes.…”

Section: Resultssupporting

confidence: 92%

Exosomes as secondary inductive signals involved in kidney organogenesis

Krause

Rak-Raszewska

Naillat

et al. 2018

J of Extracellular Vesicle

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The subfraction of extracellular vesicles, called exosomes, transfers biological molecular information not only between cells but also between tissues and organs as nanolevel signals. Owing to their unique properties such that they contain several RNA species and proteins implicated in kidney development, exosomes are putative candidates to serve as developmental programming units in embryonic induction and tissue interactions. We used the mammalian metanephric kidney and its nephron-forming mesenchyme containing the nephron progenitor/stem cells as a model to investigate if secreted exosomes could serve as a novel type of inductive signal in a process defined as embryonic induction that controls organogenesis. As judged by several characteristic criteria, exosomes were enriched and purified from a cell line derived from embryonic kidney ureteric bud (UB) and from primary embryonic kidney UB cells, respectively. The cargo of the UB-derived exosomes was analysed by qPCR and proteomics. Several miRNA species that play a role in Wnt pathways and enrichment of proteins involved in pathways regulating the organization of the extracellular matrix as well as tissue homeostasis were identified. When labelled with fluorescent dyes, the uptake of the exosomes by metanephric mesenchyme (MM) cells and the transfer of their cargo to the cells can be observed. Closer inspection revealed that besides entering the cytoplasm, the exosomes were competent to also reach the nucleus. Furthermore, fluorescently labelled exosomal RNA enters into the cytoplasm of the MM cells. Exposure of the embryonic kidney-derived exosomes to the whole MM in an ex vivo organ culture setting did not lead to an induction of nephrogenesis but had an impact on the overall organization of the tissue. We conclude that the exosomes provide a novel signalling system with an apparent role in secondary embryonic induction regulating organogenesis.

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Section: Resultssupporting

confidence: 92%

Exosomes as secondary inductive signals involved in kidney organogenesis

Krause

Rak-Raszewska

Naillat

et al. 2018

J of Extracellular Vesicle

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“…Before engineered EVs can become a therapeutic reality, their components need to be characterized in the contexts of EV heterogeneity, the dose of EVs required for a given human patient, and immune reactions [185–187]. In addition, we need to develop and standardize protocols for the large-scale production of very pure high-quality EVs, as well for efficiently loading them with therapeutic payloads [53,188]. …”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles as a platform for membrane‐associated therapeutic protein delivery

Yang

Hong

Cho

et al. 2018

J of Extracellular Vesicle

190

148

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Membrane proteins are of great research interest, particularly because they are rich in targets for therapeutic application. The suitability of various membrane proteins as targets for therapeutic formulations, such as drugs or antibodies, has been studied in preclinical and clinical studies. For therapeutic application, however, a protein must be expressed and purified in as close to its native conformation as possible. This has proven difficult for membrane proteins, as their native conformation requires the association with an appropriate cellular membrane. One solution to this problem is to use extracellular vesicles as a display platform. Exosomes and microvesicles are membranous extracellular vesicles that are released from most cells. Their membranes may provide a favourable microenvironment for membrane proteins to take on their proper conformation, activity, and membrane distribution; moreover, membrane proteins can cluster into microdomains on the surface of extracellular vesicles following their biogenesis. In this review, we survey the state-of-the-art of extracellular vesicle (exosome and small-sized microvesicle)-based therapeutics, evaluate the current biological understanding of these formulations, and forecast the technical advances that will be needed to continue driving the development of membrane protein therapeutics.

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“…Recently, EVs have come to be considered effective diagnostic and predictive tools for patients suffering from malignant tumors, such as breast and prostate cancers 32, 33. In addition to tumors, EVs show potential in the diagnosis of infectious diseases and even in the assessment of disease progression 34, 35, 36…”

Section: Introductionmentioning

confidence: 99%

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

2018

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Extracellular vesicles (EVs) are ubiquitous nanosized membrane vesicles consisting of a lipid bilayer enclosing proteins and nucleic acids, which are active in intercellular communications. EVs are increasingly seen as a vital component of many biological functions that were once considered to require the direct participation of stem cells. Consequently, transplantation of EVs is gradually becoming considered an alternative to stem cell transplantation due to their significant advantages, including their relatively low probability of neoplastic transformation and abnormal differentiation. However, as research has progressed, it is realized that EVs derived from native‐source cells may have various shortcomings, which can be corrected by modification and optimization. To date, attempts are made to modify or improve almost all the components of EVs, including the lipid bilayer, proteins, and nucleic acids, launching a new era of modularized EV therapy through the “modular design” of EV components. One high‐yield technique, generating EV mimetic nanovesicles, will help to make industrial production of modularized EVs a reality. These modularized EVs have highly customized “modular design” components related to biological function and targeted delivery and are proposed as a promising approach to achieve personalized and precision medicine.

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Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials

Cited by 1,687 publications

References 68 publications

Exosomes as secondary inductive signals involved in kidney organogenesis

Exosomes as secondary inductive signals involved in kidney organogenesis

Extracellular vesicles as a platform for membrane‐associated therapeutic protein delivery

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

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