Manufacturing Exosomes: A Promising Therapeutic Platform

Colao, Ivano; Corteling, Randolph; Bracewell, Daniel G.; Wall, Ivan

doi:10.1016/j.molmed.2018.01.006

Cited by 305 publications

(220 citation statements)

References 74 publications

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“…The size of exosomes ranges from 50 to 150 nm, whereas microvesicles and apoptotic bodies are larger vesicles ranging from 100 to 1000 and 500 to 2000 nm, respectively (2,3). ECVs have gained increasing interest as essential mediators of intercellular communication, potential biomarkers for disease conditions, and agents for the delivery of drugs and genes (1,4).…”

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confidence: 99%

Macrophage reprogramming by negatively charged membrane phospholipids controls infection

et al. 2018

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Extracellular vesicles (ECVs) are heterogeneous membrane‐enclosed structures containing proteins, nucleic acids, and lipids that participate in intercellular communication by transferring their contents to recipient cells. Although most of the attention has been directed at the biologic effect of proteins and microRNA, the contribution of phospholipids present in ECVs on cellular activation has not been extensively addressed. We investigated the biologic effect of phosphatidylserine (PS) and phosphatidylcholine (PC), 2 phospholipids highly abundant in ECVs. A transcriptomic analysis revealed that ∼4700 genes were specifically modified by exposing peritoneal macrophages to PS or PC liposomes in vivo. Among them, the expression of several chemokines and cytokines was highly upregulated by PS liposome treatment, translating into a massive neutrophil infiltration of the peritoneum capable of neutralizing a septic polymicrobial insult. Both the l and d stereoisomers of PS induced the same response, suggesting that the effect was related to the negative charge of the phospholipid head. We concluded that an increase in the internal negative charge of the cell triggers a signaling cascade activating an innate immune response capable of controlling infection.—Cauvi, D. M., Hawisher, D., Dores‐Silva, P. R., Lizardo, R. E., De, Maio, A. Macrophage reprogramming by negatively charged membrane phospholipids controls infection. FASEB J. 33, 2995–3009 (2019). http://www.fasebj.org

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confidence: 99%

Macrophage reprogramming by negatively charged membrane phospholipids controls infection

et al. 2018

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“…There are different cell culture or microenvironment conditions, including cell density, aging and passage, stage of differentiation, and substrate topography, which can greatly affect EV yield or intrinsic properties. [8] Moreover, the use of bioreactors with high cell growth surface, media recirculation, and repeated EV recovery are promising for meeting clinical standards. [9] Furthermore, implementation of routine tests of EV potency and optimal dose are of paramount importance.…”

Section: Doi: 101002/pmic201800397mentioning

confidence: 99%

“…Although the design and development of EV‐based products progresses toward standardized, controlled processes at the appropriate scale, the yield of EVs is limiting. There are different cell culture or microenvironment conditions, including cell density, aging and passage, stage of differentiation, and substrate topography, which can greatly affect EV yield or intrinsic properties . Moreover, the use of bioreactors with high cell growth surface, media recirculation, and repeated EV recovery are promising for meeting clinical standards .…”

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confidence: 99%

Toward Standardization of Mesenchymal Stromal Cell‐Derived Extracellular Vesicles for Therapeutic Use: A Call for Action

Roura

Bayés‐Genís

2018

Proteomics

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Extracellular vesicles (EVs), which include a variety of nano‐sized membrane‐encapsulated particles, are released to the extracellular microenvironment by the vast majority of cells and carry lipids, proteins, mRNA, and miRNA or non‐coding RNA. Increasing evidence suggests the great versatility and potential of EV‐based applications in humans. In this issue, van Balkom et al. explore and compare the reported proteomic signature of mesenchymal stromal cell (MSC)‐derived small EVs. In particular, their paper offers a valuable approach and point of view on MSC‐EV manufacturing and therapeutic potential. Briefly, van Balkom et al. aimed to identify a common protein signature that may be useful in ensuring the homogeneity of therapeutic MSC‐EVs. In addition to excessive variability in EV‐producing cell sources and culture conditions, the harvesting time for the EV‐containing conditioned medium, and EV isolation procedure, the authors found a specific protein signature from the publicly available MSC‐EVs proteome. In light of their findings and those from the plentiful studies published in this continuously growing area of research, potential focus areas and issues are outlined for the more rational design and optimization of MSC‐EV production and potency for therapeutics.

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“…Exosomes are nano‐membrane vesicles with 30‐100nm in size which could be released into the extracellular space through the fusion of multivesicular bodies (MVBs) and the cellular plasma membrane (Colao, Corteling, Bracewell, & Wall, ; Pegtel & Gould, ; Vlassov, Magdaleno, Setterquist, & Conrad, ). Accumulating evidence shows that exosomes are implicated to have roles in cell–cell exchange information through transfer of proteins, lipids, and RNAs.…”

Section: Introductionmentioning

confidence: 99%

Exosomes from EV71‐infected oral epithelial cells can transfer miR‐30a to promote EV71 infection

Wang¹,

Zhang

Song³

et al. 2020

Oral Diseases

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Objective As an extracellular vesicle, exosomes can release from virus‐infected cells containing various viral or host cellular elements and could stimulate recipient's cellular response. Enterovirus 71 (EV71), a single‐strand positive‐sense RNA virus, is known to cause hand, foot, and mouth disease (HFMD) in children and bring about severe clinical diseases. Methods Separated the human oral epithelial cells (OE cells) from normal buccal mucosa through enzyme digestion. Performed a comprehensive miRNA profiling in exosomes from EV71‐infected OE cells through deep small RNA‐seq. Using the Human Antiviral Response RT Profiler PCR Array profiles to explore the interactions of innate immune signaling networks with exosomal miR‐30a. Knocked out the MyD88 gene in macrophages using CRISPR/Cas9‐mediated genome editing method. Results Our study demonstrated that the miR‐30a was preferentially enriched in exosomes that released from EV71‐infected human oral epithelial cells through small RNA‐seq. We found that the transfer of exosomal miR‐30a to macrophages could suppress type Ⅰ interferon response through targeting myeloid differentiation factor 88 (MyD88) and subsequently facilitate the viral replication. Conclusions Exosomes released from EV71‐infected OE cells selectively packaged high level of miR‐30a that can be functionally transferred to the recipient macrophages resulted in targeting MyD88 and subsequently inhibited type I interferon production in receipt cells, thus promoting the EV71 replication.

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Manufacturing Exosomes: A Promising Therapeutic Platform

Cited by 305 publications

References 74 publications

Macrophage reprogramming by negatively charged membrane phospholipids controls infection

Macrophage reprogramming by negatively charged membrane phospholipids controls infection

Toward Standardization of Mesenchymal Stromal Cell‐Derived Extracellular Vesicles for Therapeutic Use: A Call for Action

Exosomes from EV71‐infected oral epithelial cells can transfer miR‐30a to promote EV71 infection

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