Camouflage strategies for therapeutic exosomes evasion from phagocytosis

Parada, Nicol; Romero-Trujillo, Alfonso; Georges, Nicolás; Alcayaga‐Miranda, Francisca

doi:10.1016/j.jare.2021.01.001

Cited by 118 publications

(123 citation statements)

References 135 publications

(222 reference statements)

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“…Camouflaging exosomes with anti-phagocytotic molecules is a feasible strategy to avoid MPS uptake, and thus extend exosomes’ half-life in circulation. Anti-phagocytotic candidate molecules that can be inserted or expressed on the surface of exosomes include CD47, CD24, CD44, CD31, β2M, PD-L1, App1, and DHMEQ ( Parada et al, 2021 ). The time EVs stayed in the plasma doubled after CD47 modification, and improved biodistribution in targeted tissue was observed ( Wei et al, 2021 ).…”

Section: Clinical Translation Of Exosome Therapymentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosome Therapy of Microbial Diseases: From Bench to Bed

Wu¹,

Jin²,

Ding³

et al. 2022

Front. Microbiol.

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Microbial diseases are a global health threat, leading to tremendous casualties and economic losses. The strategy to treat microbial diseases falls into two broad categories: pathogen-directed therapy (PDT) and host-directed therapy (HDT). As the typical PDT, antibiotics or antiviral drugs directly attack bacteria or viruses through discerning specific molecules. However, drug abuse could result in antimicrobial resistance and increase infectious disease morbidity. Recently, the exosome therapy, as a HDT, has attracted extensive attentions for its potential in limiting infectious complications and targeted drug delivery. Mesenchymal stem cell-derived exosomes (MSC-Exos) are the most broadly investigated. In this review, we mainly focus on the development and recent advances of the application of MSC-Exos on microbial diseases. The review starts with the difficulties and current strategies in antimicrobial treatments, followed by a comprehensive overview of exosomes in aspect of isolation, identification, contents, and applications. Then, the underlying mechanisms of the MSC-Exo therapy in microbial diseases are discussed in depth, mainly including immunomodulation, repression of excessive inflammation, and promotion of tissue regeneration. In addition, we highlight the latest progress in the clinical translation of the MSC-Exo therapy, by summarizing related clinical trials, routes of administration, and exosome modifications. This review will provide fundamental insights and future perspectives on MSC-Exo therapy in microbial diseases from bench to bedside.

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Section: Clinical Translation Of Exosome Therapymentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosome Therapy of Microbial Diseases: From Bench to Bed

Wu¹,

Jin²,

Ding³

et al. 2022

Front. Microbiol.

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“…More importantly, exosomes, as cell-free therapy, possess enhanced delivery of exogenous biological particles to the target site and directly into the cytosol, circumventing the lysosomal-endosomal pathway, and consequently elevating transfection efficiency (Wu et al, 2020). As a result of their small sizes and other camouflage strategies, exosomes are capable of evading the mononuclear phagocytic system's clearance, leading to extended circulatory time for passive targeting of inflammatory and cancerous cells (Belhadj et al, 2020;Parada et al, 2021). In comparison to their parent cells, these extracellular vesicles are more stable and could reduce the inherent safety risks associated with the administration of cell-based therapy, including the risk of occlusion in the microvasculature, as well as possible immune recognition by the host system (Nikfarjam et al, 2020).…”

Section: Main Textmentioning

confidence: 99%

Mesenchymal stem cell-derived exosome: The likely game-changer in stem cell research

Ocansey¹,

Xu²,

ZHANG³

et al. 2022

Biocell

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Stem cell research is a promising area of transplantation and regenerative medicine with tremendous potential for improving the clinical treatment and diagnostic options across a variety of conditions and enhancing understanding of human development. Over the past few decades, mesenchymal stem cell (MSCs) studies have exponentially increased with a promising outcome. However, regardless of the huge investment and the research attention given to stem cell research, FDA approval for clinical use is still lacking. Amid the challenges confronting stem cell research as a cellbased product, there appears to be evidence of superior effect and heightened potential success in its expressed vesicles, exosomes, as cell-free products. In addition to their highly desirable intrinsic biologically unique structural, compositional, and morphological characteristics, as well as predominant physiochemical stability and biocompatibility properties, exosomes can also be altered to enhance their therapeutic capability or diagnostic imaging potential via physical, chemical, and biological modification approaches. More importantly, the powerful therapeutic potential and superior biological functions of exosomes, particularly, regarding engineered exosomes as cell-free products, and their utilization in a new generation of nanomedicine treatment, vaccination, and diagnosis platforms, brings hope of a change in the near future. This viewpoint discusses the trend of stem cell research and why stem cell-derived exosomes could be the game-changer.

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“…EVs, on the other hand, can evade removal by immune cells naturally. CD47 is a prominent component found on EVs that binds to signal regulatory protein alpha (SIRPα) on dendritic cells and macrophages, which inhibits phagocytosis via a "don't eat me" signal [129][130][131]. Other EV components found on both cancer and non-cancer cell-derived EVs like CD24, CD31 and PD-L1 have been associated with exerting a similar "don't eat me" signal, with PD-L1 also inhibiting T-cell activation [130,[132][133][134].…”

Section: Immunological Barriersmentioning

confidence: 99%

“…Natural evasion of immune cells is a highly favourable quality and should mark all engineered EVs regardless of the barrier(s) they target. CD47, CD24, CD31 and PD-L1 are prominent surface proteins that achieve this quality and should be incorporated into engineered EVs in high amounts if not originally present [129][130][131][132][133][134]. Fusing EVs with liposomes to create hybrid DDSs can also increase their drug loading capacity without risking cargo aggregation [198,199].…”

Section: Recommendation-evs As Drug Carriersmentioning

confidence: 99%

Extracellular Vesicles and Their Interplay with Biological Membranes

Ping¹,

Neupane²,

Pastorin³

2022

Extracellular Vesicles - Role in Diseases, Pathogenesis and Therapy

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Most cells secrete vesicles into the extracellular environment to interact with other cells. These extracellular vesicles (EVs), have undergone a paradigm shift upon the discovery that they also transport important material including proteins, lipids and nucleic acids. As natural cargo carriers, EVs are not recognised by the immune system as foreign substances, and consequently evade removal by immune cells. These intrinsic biological properties of EVs have led to further research on utilising EVs as potential diagnostic biomarkers and drug delivery systems (DDSs). However, the internalisation of EVs by target cells is still not fully understood. Moreover, it is unclear whether EVs can cross certain biological membranes like the blood-brain barrier (BBB) naturally, or require genetic modifications to do so. Hence, this review aims to evaluate the relationship between the composition of EVs and their association with different biological membranes they encounter before successfully releasing their cargo into target cells. This review identifies specific biomarkers detected in various EVs and important biological barriers present in the gastrointestinal, placental, immunological, neurological, lymphatic, pulmonary, renal and intracellular environments, and provides a recommendation on how to engineer EVs as potential drug carriers based on key proteins and lipids involved in crossing these barriers.

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Camouflage strategies for therapeutic exosomes evasion from phagocytosis

Abstract: Graphical abstract

Cited by 118 publications

References 135 publications

Mesenchymal Stem Cell-Derived Exosome Therapy of Microbial Diseases: From Bench to Bed

Mesenchymal Stem Cell-Derived Exosome Therapy of Microbial Diseases: From Bench to Bed

Mesenchymal stem cell-derived exosome: The likely game-changer in stem cell research

Extracellular Vesicles and Their Interplay with Biological Membranes

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