Shedding Light on Extracellular Vesicle Biogenesis and Bioengineering

Teng, Fei; Fussenegger, Martin

doi:10.1002/advs.202003505

Cited by 252 publications

(234 citation statements)

References 259 publications

(464 reference statements)

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“…Eukaryotic cells spontaneously release vesicles of different sizes including apoptotic bodies (1–5 μm), microvesicles (50–1000 nm), and exosomes (50–200 nm) [ 1 ]. Microvesicles (also referred to as ectosomes) shed by plasma membrane, whereas exosomes are released after inward invagination of endosome membranes and the formation of intraluminal vesicles.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Antitumor CD8+ T Cell Immunity Induced by Endogenously Engineered Extracellular Vesicles

Ferrantelli

Manfredi

Chiozzini

et al. 2021

Cancers

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We developed an innovative method to induce antigen-specific CD8+ T cytotoxic lymphocyte (CTL) immunity based on in vivo engineering of extracellular vesicles (EVs). This approach employs a DNA vector expressing a mutated HIV-1 Nef protein (Nefmut) deprived of the anti-cellular effects typical of the wild-type isoform, meanwhile showing an unusual efficiency of incorporation into EVs. This function persists even when foreign antigens are fused to its C-terminus. In this way, Nefmut traffics large amounts of antigens fused to it into EVs spontaneously released by the recipient cells. We previously provided evidence that mice injected with a DNA vector expressing the Nefmut/HPV16-E7 fusion protein developed an E7-specific CTL immune response as detected 2 weeks after the second immunization. Here, we extended and optimized the anti-HPV16 CD8+ T cell immune response induced by the endogenously engineered EVs, and evaluated the therapeutic antitumor efficacy over time. We found that the co-injection of DNA vectors expressing Nefmut fused with E6 and E7 generated a stronger anti-HPV16 immune response compared to that observed in mice injected with the single vectors. When HPV16-E6 and -E7 co-expressing tumor cells were implanted before immunization, all mice survived at day 44, whereas no mice injected with either void or Nefmut-expressing vectors survived until day 32 after tumor implantation. A substantial part of immunized mice (7 out of 12) cleared the tumor. When the cured mice were re-challenged with a second tumor cell implantation, none of them developed tumors. Both E6- and E7-specific CD8+ T immunities were still detectable at the end of the observation time. We concluded that the immunity elicited by engineered EVs, besides counteracting and curing already developed tumors, was strong enough to guarantee the resistance to additional tumor attacks. These results can be of relevance for the therapy of both metastatic and relapsing tumors.

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Section: Introductionmentioning

confidence: 99%

Long-Term Antitumor CD8+ T Cell Immunity Induced by Endogenously Engineered Extracellular Vesicles

Ferrantelli

Manfredi

Chiozzini

et al. 2021

Cancers

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“…In addition, exosome-mediated intercellular communication has been shown to require docking on the plasma membrane in an earlier study (Teng and Fussenegger, 2021). Also, integrins, lipids, heparan sulfate proteoglycans, and ECM components (especially FN and laminin) can function as mediators in the intercellular interaction (van Niel et al, 2018).…”

Section: Discussionmentioning

confidence: 96%

Salidroside Inhibits CCl4-Induced Liver Fibrosis in Mice by Reducing Activation and Migration of HSC Induced by Liver Sinusoidal Endothelial Cell-Derived Exosomal SphK1

Zhou

Zhao

et al. 2021

Front. Pharmacol.

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Sphingosine kinase 1 (SphK1)/Sphingosine-1-phosphate (S1P)/S1PRs signaling pathway is known to involve the advancement of liver fibrosis. Exosomal SphK1 promotes hepatic stellate cells (HSC) migration. Salidroside (Sal) inhibits liver fibrosis, but its mechanism is yet to be elucidated. This study was to explore the influences of Sal on the SphK/S1P/S1PRs signaling pathway in liver fibrosis induced by carbon tetrachloride (CCl4) in vivo, and investigated the mechanism of Sal affecting the migration and activation of HSC triggered by exosomal SphK1 in vitro. Our data showed that Sal reduced the activities of alanine transaminase (ALT), aspartate aminotransferase (AST) in serum, and hydroxyproline (Hyp) content in the liver tissue. Sal subdued the expression of α-smooth muscle actin (α-SMA), fibronectin (FN) and type I collagen (Col I) of the liver. Sal also reduced mitochondria-induced hepatocyte apoptosis and to inhibit JNK activation. Furthermore, Sal remarkably eradicated the influence of SphK1, SphK2, S1P, and S1PRs triggered by CCl4, whether stimulating or hindering. Compared with serum-derived exosomes from model group mice, serum-derived exosomes from Sal group mice expressed lower SphK1 and reduced JS 1 (mouse HSC cell line) migration. In addition, Sal was also observed to subdue Col I expression, AKT activation, and LX-2 migration induced by exosomal SphK1 from SK-HEP-1 (a kind of liver sinusoidal endothelial cells (LSEC) cell line). In conclusion, Sal could effectively alleviate liver injury, hepatocyte apoptosis, and liver fibrosis in vivo, providing supports that the protective effects of Sal might be realized by suppressing JNK activation and modulating the SphK/S1P/S1PRs axis. In vitro, it was observed that Sal might alleviate LX-2 migration and activation induced by exosomal SphK1 by inhibiting the AKT activation.

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“…The extracellular space of multi-cellular organisms contains solutions composed of metabolites, ions, proteins and polysaccharides, but also of a wide range of membraneenclosed vesicles, henceforward referred as to "extracellular vesicles" (EV). EV are cellderived sub-micronic vesicles released into the extracellular space in both normal and pathological conditions [1][2][3][4][5]. The importance of EV production in the living world has long been underestimated, with EV considered as irrelevant platelet residues or "cell dust" and initially discarded from studies [6].…”

Section: Extracellular Vesicles: An Overviewmentioning

confidence: 99%

The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma

Marimpietri

Airoldi

Faini

et al. 2021

IJMS

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The long-underestimated role of extracellular vesicles in cancer is now reconsidered worldwide by basic and clinical scientists, who recently highlighted novel and crucial activities of these moieties. Extracellular vesicles are now considered as king transporters of specific cargoes, including molecular components of parent cells, thus mediating a wide variety of cellular activities both in normal and neoplastic tissues. Here, we discuss the multifunctional activities and underlying mechanisms of extracellular vesicles in neuroblastoma, the most frequent common extra-cranial tumor in childhood. The ability of extracellular vesicles to cross-talk with different cells in the tumor microenvironment and to modulate an anti-tumor immune response, tumorigenesis, tumor growth, metastasis and drug resistance will be pinpointed in detail. The results obtained on the role of extracellular vesicles may represent a panel of suggestions potentially useful in practice, due to their involvement in the response to chemotherapy, and, moreover, their ability to predict resistance to standard therapies—all issues of clinical relevance.

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Shedding Light on Extracellular Vesicle Biogenesis and Bioengineering

Cited by 252 publications

References 259 publications

Long-Term Antitumor CD8+ T Cell Immunity Induced by Endogenously Engineered Extracellular Vesicles

Long-Term Antitumor CD8+ T Cell Immunity Induced by Endogenously Engineered Extracellular Vesicles

Salidroside Inhibits CCl4-Induced Liver Fibrosis in Mice by Reducing Activation and Migration of HSC Induced by Liver Sinusoidal Endothelial Cell-Derived Exosomal SphK1

The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma

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