Extracellular Vesicle-Mediated Bilateral Communication between Glioblastoma and Astrocytes

Nieland, Lisa; Morsett, Liza M.; Broekman, Marike L. D.; Breakefield, Xandra O.; Abels, Erik R.

doi:10.1016/j.tins.2020.10.014

Cited by 53 publications

(49 citation statements)

References 90 publications

(113 reference statements)

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“…Accumulating data suggest that EVs alter the pro-inflammatory properties of microglia [70], including a shift into M2anti-inflammatory conditions [71]. Additionally, it has been shown recently that microglia and astrocytes communicate in part via the release of EVs from microglia [72]. It is an intriguing possibility that, in vivo, microglia or astrocytes released the administered EVs for later uptake into RGCs, although in our present study, we cannot make any conclusions on this possible exchange mechanism.…”

Section: Discussionmentioning

confidence: 53%

Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Mathew

Torres

Gamboa

et al. 2021

Cells

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Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

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Section: Discussionmentioning

confidence: 53%

Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Mathew

Torres

Gamboa

et al. 2021

Cells

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“…In the central nervous system, EVs have been found to play a crucial role in intercellular communication in both physiological and pathological conditions. For example, in brain tumors, astrocyte-derived EVs are involved in reciprocal crosstalk with glioblastoma (GBM) cells [ 62 ] which may mediate pro- or antitumor roles of astrocytes in tumor development. Another study broadened the functional role of astrocytes showing that upon activation by interleukins, these cells could affect neuronal uptake, differentiation, and firing via enrichment of surface membrane proteins such as integrins and the major histocompatibility complex [ 63 ].…”

Section: Ev Targetingmentioning

confidence: 99%

Fostering “Education”: Do Extracellular Vesicles Exploit Their Own Delivery Code?

Paolillo

Comincini

Schinelli

2021

Cells

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Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has so far mainly been investigated as a function of EX cargo, while few studies have focused on the characterization of EV surface membrane molecules and the mechanisms that mediate the addressability of specific EVs to different cell types and tissues. Identifying these mechanisms will help fulfill the diagnostic, prognostic, and therapeutic promises fueled by our growing knowledge of EVs. In this review, we first discuss published studies on the presumed EV “delivery code” and on the combinations of the hypothesized EV surface membrane “sender” and “recipient” molecules that may mediate EV targeting in intercellular communication. Then we briefly review the main experimental approaches and techniques, and the bioinformatic tools that can be used to identify and characterize the structure and functional role of EV surface membrane molecules. In the final part, we present innovative techniques and directions for future research that would improve and deepen our understandings of EV-cell targeting.

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“…During this time, proteins, nucleic acids, and lipids are screened and enter the intraluminal vesicles. Late endosomes containing a large number of intraluminal vesicles are also called multivesicular bodies (Zhang et al, 2020 ; Nieland et al, 2021 ). Multivesicular bodies have two metabolic pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Exosomes carry various bioactive compounds as cargo, such as proteins, non-coding RNAs, lipids, etc. after being secreted from cells, thus facilitating communication between cells (Nieland et al, 2021 ). This function of exosomes forms the basis for their role in the development of various diseases, and altering the cargoes carried by exosomes or changing their surface molecules may hold therapeutic potential (Jafari et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Role of Exosomes in Brain Diseases

Zhang

Chen

et al. 2021

Front. Cell. Neurosci.

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Exosomes are a subset of extracellular vesicles that act as messengers to facilitate communication between cells. Non-coding RNAs, proteins, lipids, and microRNAs are delivered by the exosomes to target molecules (such as proteins, mRNAs, or DNA) of host cells, thereby playing a key role in the maintenance of normal brain function. However, exosomes are also involved in the occurrence, prognosis, and clinical treatment of brain diseases, such as Alzheimer's disease, Parkinson's disease, stroke, and traumatic brain injury. In this review, we have summarized novel findings that elucidate the role of exosomes in the occurrence, prognosis, and treatment of brain diseases.

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Extracellular Vesicle-Mediated Bilateral Communication between Glioblastoma and Astrocytes

Cited by 53 publications

References 90 publications

Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Fostering “Education”: Do Extracellular Vesicles Exploit Their Own Delivery Code?

Role of Exosomes in Brain Diseases

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