Exosomes: biogenesis, biologic function and clinical potential

Zhang, Yuan; Liu, Yunfeng; Liu, Haiying; Tang, Wai Ho

doi:10.1186/s13578-019-0282-2

Cited by 1,518 publications

(1,385 citation statements)

References 155 publications

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“…Within the ESCRT system, endosomes and intraluminal vesicles are formed at MVBs and are either transported to lysosomes for degradation or exocytosed as exosomes through the plasma membrane via calcium-dependent mechanisms. 12 Canonical markers for exosomes include tetraspanins and plasma membrane proteins, such as tetraspanins (CD9 and CD63), Alix, and TSG101. 13 An additional subpopulation of EVs, distinct from exosomes in genesis and content are microvesicles, with diameters ranging from 100 nm to 1 μm.…”

mentioning

confidence: 99%

Analysis of Adult Neural Retina Extracellular Vesicle Release, RNA Transport and Proteomic Cargo

Mighty

Zhou

Benito-Martín

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Citation: Mighty J, Zhou J, Benito-Martin A, et al. Analysis of adult neural retina extracellular vesicle release, RNA transport and proteomic cargo. Invest Ophthalmol Vis Sci. 2020;61(2):30. https://doi.org/10.1167/iovs.61.2.30 PURPOSE. Extracellular vesicles (EVs) contain RNA and protein cargo reflective of the genotype and phenotype of the releasing cell of origin. Adult neural retina EV release, RNA transfer, and proteomic cargo are the focus of this study. METHODS. Adult wild-type mouse retinae were cultured and released EV diameters and concentrations quantified using Nanosight. Immunogold transmission electron microscopy (TEM) was used to image EV ultrastructure and marker protein localization. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze retinal cell transcripts present in EVs. Super-resolution microscopy was used to image fluorescent (green) RNA and (red) lipid membrane labeled EVs, released by adult retina, and internalized by isolated retinal cells. Mass spectrometry was used to characterize the proteomes of adult retina and EVs. RESULTS. Adult neural retina released EVs at a rate of 1.42 +/− 0.08 × 10 8 /mL over 5 days, with diameters ranging from 30 to 910 nm. The canonical EV markers CD63 and Tsg101 localized to retinal EVs. Adult retinal and neuronal mRNA species present in both retina and EVs included rhodopsin and the neuronal nuclei marker NeuN. Fluorescently labeled RNA in retinal cells was enclosed in EVs, transported to, and uptaken by cocultured adult retinal cells. Proteomic analysis revealed 1696 protein species detected only in retinal cells, 957 species shared between retina and EVs, and 82 detected only in EVs.CONCLUSIONS. The adult neural retina constitutively releases EVs with molecular cargo capable of intercellular transport and predicted involvement in biological processes including retinal physiology, mRNA processing, and transcription regulation within the retinal microenvironment.

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mentioning

confidence: 99%

Analysis of Adult Neural Retina Extracellular Vesicle Release, RNA Transport and Proteomic Cargo

Mighty

Zhou

Benito-Martín

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…Unfortunately, validated, commercially available, canine‐specific ELISAs for additional variants and isoforms are not currently available. Another possible study direction could be the evaluation of VEGF, mRNA and/or protein circulating in serum/plasma exosomes …”

Section: Discussionmentioning

confidence: 99%

“…Another possible study direction could be the evaluation of VEGF, mRNA and/or protein circulating in serum/ plasma exosomes. [24][25][26]…”

Section: Discussionmentioning

confidence: 99%

Noninvasive evaluation of vascular endothelial growth factor‐A (VEGF‐A) protein concentrations in the stratum corneum and serum of healthy and atopic dogs

Cobiella

Gram

Santoro

2019

Veterinary Dermatology

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Background Vascular endothelial growth factor (VEGF) is a cytokine involved primarily in angiogenesis. In human atopic dermatitis (AD), VEGF has been detected in the stratum corneum and blood. Objective To evaluate VEGF‐A expression in the serum and stratum corneum of healthy and atopic dogs, and its possible correlation with disease severity in atopic dogs. Animal Fifteen atopic and 15 healthy, privately owned dogs. Methods and materials The severity of clinical signs associated with AD was evaluated with the Canine Atopic Dermatitis Extent and Severity Index (CADESI‐04). For all dogs, a single blood sample was performed and serum collected. Tape stripping (15 times) was performed on the left periocular area (lesional skin). A commercially available canine‐specific VEGF‐A enzyme‐linked immunosorbent assay was performed with all samples. Results Vascular endothelial growth factor‐A was undetectable in the serum. In the stratum corneum, there was no significant difference in VEGF‐A concentrations between healthy (mean 89.4 ± 59.5 pg/ml) and atopic dogs (mean 100.3 ± 77.1pg/ml) (P = 0.71). There was no correlation between stratum corneum VEGF‐A concentrations and CADESI‐04 scores. Conclusions and clinical importance The role of VEGF in canine AD is unclear. Because of many variants, VEGF‐C and VEGF‐D or VEGF‐A isotopes should be explored in the skin to better evaluate the role of VEGF in canine atopy. Full‐thickness skin biopsy, molecular biology and histopathological investigation may be necessary to further assess cutaneous VEGF expression.

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“…Exosomes are produced with the plasma membrane following the fusion of multivesicular bodies (MVB), which are endocytic organelles comprising many luminal vesicles. MVs and apoptotic bodies, on the contrary, are formed by direct external budding from the plasma membrane (Zhang et al, 2019).…”

Section: Evsmentioning

confidence: 99%

Mesenchymal stromal cell‐derived extracellular vesicles as cell‐free biologics for the ex vivo expansion of hematopoietic stem cells

Budgude

Kale

Vaidya

2020

Cell Biology International

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Hematopoietic stem cell transplantation (HSCT) is the ultimate choice of treatment for patients with hematological diseases and cancer. The success of HSCT is critically dependent on the number and engraftment efficiency of the transplanted donor hematopoietic stem cells (HSCs). Various studies show that bone marrow-derived mesenchymal stromal cells (MSCs) support hematopoiesis and also promote ex vivo expansion of HSCs. MSCs exert their therapeutic effect through paracrine activity, partially mediated through extracellular vesicles (EVs). Although the physiological function of EVs is not fully understood, inspiring findings indicate that MSC-derived EVs can reiterate the hematopoiesis, supporting the ability of MSCs by transferring their cargo containing proteins, lipids, and nucleic acids to the HSCs. The activation state of the MSCs or the signaling mechanism that prevails in them also defines the composition of their EVs, thereby influencing the fate of HSCs. Modulating or preconditioning MSCs to achieve a specific composition of the EV cargo for the ex vivo expansion of HSCs is, therefore, a promising strategy that can overcome several challenges associated with the use of naïve/unprimed MSCs. This review aims to speculate upon the potential role of preconditioned/primed MSC-derived EVs as "cell-free biologics," as a novel strategy for expanding HSCs in vitro.

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Exosomes: biogenesis, biologic function and clinical potential

Cited by 1,518 publications

References 155 publications

Analysis of Adult Neural Retina Extracellular Vesicle Release, RNA Transport and Proteomic Cargo

Analysis of Adult Neural Retina Extracellular Vesicle Release, RNA Transport and Proteomic Cargo

Noninvasive evaluation of vascular endothelial growth factor‐A (VEGF‐A) protein concentrations in the stratum corneum and serum of healthy and atopic dogs

Mesenchymal stromal cell‐derived extracellular vesicles as cell‐free biologics for the ex vivo expansion of hematopoietic stem cells

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