Extracellular Vesicles in neural cell interaction and CNS homeostasis

Schnatz, Andrea; Müller, Christina; Brahmer, Alexandra; Krämer-Albers, Eva-Maria

doi:10.1096/fba.2021-00035

Cited by 57 publications

(48 citation statements)

References 162 publications

(216 reference statements)

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“…Intricate interactions between neurons and glia are a prerequisite for normal function of the nervous system (Figure 4) [100]. Communication in the CNS has been described as multimodal and categorized into wiring transmission (one on one transmission) and volume transmission (one to many transmission) [101].…”

Section: Role Of Exosomes In the Central Nervous System (Cns)mentioning

confidence: 99%

Small but Mighty—Exosomes, Novel Intercellular Messengers in Neurodegeneration

Kumari

Anji

2022

Biology

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Exosomes of endosomal origin are one class of extracellular vesicles that are important in intercellular communication. Exosomes are released by all cells in our body and their cargo consisting of lipids, proteins and nucleic acids has a footprint reflective of their parental origin. The exosomal cargo has the power to modulate the physiology of recipient cells in the vicinity of the releasing cells or cells at a distance. Harnessing the potential of exosomes relies upon the purity of exosome preparation. Hence, many methods for isolation have been developed and we provide a succinct summary of several methods. In spite of the seclusion imposed by the blood–brain barrier, cells in the CNS are not immune from exosomal intrusive influences. Both neurons and glia release exosomes, often in an activity-dependent manner. A brief description of exosomes released by different cells in the brain and their role in maintaining CNS homeostasis is provided. The hallmark of several neurodegenerative diseases is the accumulation of protein aggregates. Recent studies implicate exosomes’ intercellular communicator role in the spread of misfolded proteins aiding the propagation of pathology. In this review, we discuss the potential contributions made by exosomes in progression of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Understanding contributions made by exosomes in pathogenesis of neurodegeneration opens the field for employing exosomes as therapeutic agents for drug delivery to brain since exosomes do cross the blood–brain barrier.

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Section: Role Of Exosomes In the Central Nervous System (Cns)mentioning

confidence: 99%

Small but Mighty—Exosomes, Novel Intercellular Messengers in Neurodegeneration

Kumari

Anji

2022

Biology

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“…Extracellular vesicles (EVs) are a heterogeneous group of nano- to micro-sized membrane-enclosed particles that are found in almost every sample of biological origin [ 1 ]. They function as a means of intercellular communication [ 1 , 2 , 3 , 4 ] and are involved in several physiological and pathological contexts, such as in embryogenesis [ 5 , 6 , 7 , 8 , 9 ], neuronal communication [ 10 ], blood coagulation [ 11 , 12 ], inflammation [ 13 , 14 ], tumorigenesis [ 1 , 15 ], and horizontal gene transfer [ 7 , 8 , 16 ]. In recent decades, EVs have been extensively studied for their potential clinical utility: as biomarkers to track the progression of various diseases, as drugs, or as vectors for drug-delivery [ 4 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Stability of Erythrocyte-Derived Nanovesicles Assessed by Light Scattering and Electron Microscopy

Božič

Hočevar

Kisovec

et al. 2021

IJMS

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Extracellular vesicles (EVs) are gaining increasing amounts of attention due to their potential use in diagnostics and therapy, but the poor reproducibility of the studies that have been conducted on these structures hinders their breakthrough into routine practice. We believe that a better understanding of EVs stability and methods to control their integrity are the key to resolving this issue. In this work, erythrocyte EVs (hbEVs) were isolated by centrifugation from suspensions of human erythrocytes that had been aged in vitro. The isolate was characterised by scanning (SEM) and cryo-transmission electron microscopy (cryo-TEM), flow cytometry (FCM), dynamic/static light scattering (LS), protein electrophoresis, and UV-V spectrometry. The hbEVs were exposed to various conditions (pH (4–10), osmolarity (50–1000 mOsm/L), temperature (15–60 °C), and surfactant Triton X-100 (10–500 μM)). Their stability was evaluated by LS by considering the hydrodynamic radius (Rh), intensity of scattered light (I), and the shape parameter (ρ). The morphology of the hbEVs that had been stored in phosphate-buffered saline with citrate (PBS–citrate) at 4 °C remained consistent for more than 6 months. A change in the media properties (50–1000 mOsm/L, pH 4–10) had no significant effect on the Rh (=100–130 nm). At pH values below 6 and above 8, at temperatures above 45 °C, and in the presence of Triton X-100, hbEVs degradation was indicated by a decrease in I of more than 20%. Due to the simple preparation, homogeneous morphology, and stability of hbEVs under a wide range of conditions, they are considered to be a suitable option for EV reference material.

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“…The latter could be observed if EV’s are not cleared in an immunologically silent process but instead when it leads to macrophage activation. Such activation most likely depends on the EV-contained cargo and the state of the donor cell, as discussed recently in the case of microglia ( Schnatz et al, 2021 ). Additionally, one can speculate that macrophages in inflamed tissue are possibly more prone to undergo unexpected activation after EV’s engulfment.…”

Section: Challenges In Therapeutic Application Of Extracellular Vesiclesmentioning

confidence: 84%

“…Furthermore, resident macrophages are considered to clear EVs also in other tissues. For instance, microglia can phagocytose and thus remove EVs from the brain parenchyma ( Schnatz et al, 2021 ). Thus, fast clearance by macrophages not only hampers EV’s delivery to desired tissue and target cell population, but also may either affect the expected therapeutic action or cause some side effects.…”

Section: Challenges In Therapeutic Application Of Extracellular Vesiclesmentioning

confidence: 99%

Increasing the Therapeutic Efficacy of Extracellular Vesicles From the Antigen-Specific Antibody and Light Chain Perspective

Nazimek

Bryniarski

2021

Front. Cell Dev. Biol.

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Due to their exceptional properties, extracellular vesicles (EVs) receive special attention as next generation biotherapeutics and vehicles for drug delivery. However, despite having many advantages over cell-based therapies, EVs usually exert lower therapeutic efficacy. This results from a number of hurdles that are faced by the EV-based approaches. Administered EVs could be rapidly cleared by the mononuclear phagocytes as well as can randomly distribute within various tissues, making tissue penetration and cell targeting insufficient. However, recent research findings imply that these limitations could be overcome with the use of antigen-specific antibodies and light chains. Major histocompatibility complex (MHC) class II-expressing EVs have been shown to form aggregates after co-incubation with antigen-specific antibodies, which greatly enhanced their biological efficacy. On the other hand, EVs could be coated with antibody light chains of chosen specificity to direct them towards desired target cell population. Both findings open up a promising perspective to achieve the highest efficacy of the EV-based approaches. Herein we discuss the opportunities for enhancing extracellular vesicle’s biological activity by using specific antibodies and light chains in the context of the challenges faced by such therapeutic approach.

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Extracellular Vesicles in neural cell interaction and CNS homeostasis

Cited by 57 publications

References 162 publications

Small but Mighty—Exosomes, Novel Intercellular Messengers in Neurodegeneration

Small but Mighty—Exosomes, Novel Intercellular Messengers in Neurodegeneration

Stability of Erythrocyte-Derived Nanovesicles Assessed by Light Scattering and Electron Microscopy

Increasing the Therapeutic Efficacy of Extracellular Vesicles From the Antigen-Specific Antibody and Light Chain Perspective

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