Journal of Extracellular Vesicles最新文献

Extracellular vesicles (EVs) have emerged as powerful mediators of intercellular communication with significant potential across biomedical, veterinary, cosmetic, agricultural and environmental applications. However, the translation of EV-based discoveries into practical and commercially viable products remains constrained by scientific complexity, regulatory uncertainty and manufacturing challenges. To address these barriers, the International Society for Extracellular Vesicles (ISEV) established the Translation, Regulation and Advocacy Committee (ISEV-TRA). ISEV-TRA aims to catalyse the responsible advancement of EV technologies by fostering cross-sector collaboration, harmonising quality and regulatory frameworks and providing strategic advocacy to enhance market readiness. Through targeted initiatives—such as workshops and the development of translational resources and guidance—ISEV-TRA seeks to bridge the gap between research and real-world implementation. By promoting dialogue amongst academia, industry, investors and policymakers, ISEV-TRA positions itself as a central driver in shaping the global roadmap for EV translation and commercialisation.

Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease characterized by aberrant myofibroblast activation and excessive extracellular matrix deposition, with extracellular vesicles (EVs) playing a crucial role in this pathological process. We observed that EVs levels are significantly elevated in IPF and positively correlate with nestin expression, a known marker of lung myofibroblasts. These myofibroblast-derived EVs further amplify profibrotic responses, creating a self-perpetuating cycle. To elucidate the mechanisms driving increased EVs secretion, we conducted in vitro and in vivo experiments, demonstrating that nestin knockdown not only suppresses EVs release but also impairs their ability to promote TGF-β-induced myofibroblast differentiation. Mechanistically, nestin recruits TBC1D15 to inactivate Rab7, thereby inhibiting multivesicular body (MVB) degradation and enhancing EVs secretion. Importantly, pharmacological activation of Rab7 using ML-098 significantly attenuated pulmonary fibrosis in mouse models. Our findings establish the Nestin-Rab7 axis as a key regulator of EVs-mediated fibrotic signaling and highlight its therapeutic potential for IPF treatment.

Oncolytic adenoviruses (OVs) can directly eliminate cancer cells and subsequently activate immune responses, exhibiting potent antitumor therapeutics. However, it was observed that the immune cells can also be lysed during viral treatment, evidently dampening the OVs-mediated antitumor immune response. In this study, we develop a microneedle (MN)-based in situ tumor cell-derived extracellular nanovesicle (TDEV)-cloaked OVs platform to enhance cancer immunotherapy and reduce immune cell exhaustion. In this platform, tumor cells pre-infected with OVs are loaded into the upper reservoir of the MN device. Following the transdermal administration, the hollow MN would constantly facilitate the transport of in situ the generated TDEV-encapsulating OVs into the tumor site for sustained delivery of OVs, which could subsequently infect cancer cells selectively rather than immune cells. Enhanced antigens triggered by improved intratumoral OVs killing can be presented by non-exhausted dendritic cells, further evoking significant immunotherapeutic effects in both TC-1-hCD46 xenograft tumor-bearing mice and postoperative tumor recurrence mice models.

As a novel identified manner of cell death, NETosis is widely regarded as an effective approach to resist pathogen infection but mainly focused on vertebrates with systematic cell typing. Besides, the role of extracellular vesicles (EVs), which are essential tools for intercellular information exchange, in regulating NETosis during pathogen infection has yet to be addressed. Here, we found that viral mRNA wsv271 could be packaged by EVs secreted by haemocytes during WSSV infection in mud crab, and delivered to the neutrophil-like cells, followed by translation into viral protein, and then interacted with the TIR domain of Toll4 to recruit MyD88, so as to activate P38-MAPK signal pathway and further facilitate PAD4 phosphorylation and nuclear translocation to mediate histone-H3 citrullination, which eventually activated NETosis-like response in haemocytes to suppress the spread of viral infection. Therefore, our research not only identified neutrophil-like cells from the haemocytes of a crustacean based on single-cell transcriptomics but also revealed a novel NETosis induction mechanism mediated by EVs-derived viral nucleic acid delivery.

Tan, J., Y. Hu, L. Zheng, et al. 2025. “Microbead Encapsulation Strategy for Efficient Production of Extracellular Vesicles Derived From Human Mesenchymal Stem Cells.” Journal of Extracellular Vesicles 14, no. 4: e70053. https://doi.org/10.1002/jev2.70053.

The footnote of this article has been updated to read Jiayi Tan, Yunxia Hu, and Lijuan Zheng contributed equally to this work. This was left out of an earlier corrected version of this article. The online version of this article has been corrected.

We apologize for this error.

Proteolysis targeting chimeras (PROTACs) represent an emerging targeted cancer therapy approach. However, their poor cell penetration and instability in vivo pose daunting challenges for wide-spread clinical usage. To enhance the in vivo therapeutic efficacy of PROTACs, we introduced extracellular vesicles (EVs) for in vivo PROTAC delivery, which is leveraged by a novel microfluidic droplet-based EV electro-transfection system (μDES). We previously developed YX968 PROTAC, which can selectively degrade both HDAC3 and HDAC8 in triple negative breast cancer (TNBC) cells and effectively suppress the tumour cell growth without provoking global hyperacetylation. In this manuscript, we demonstrated that YX968 loaded EVs via the μDES system can retain the optimal integrity of drug loaded EVs with improved loading efficiency compared to other transfection approaches, which, in turn, significantly enhances the therapeutic function of PROTAC in vivo in TNBC mouse models. Intraperitoneal injections of YX968 loaded EVs led to significantly enhanced intratumoral degradation of HDAC3 and HDAC8 than YX986 alone, which resulted in advanced TNBC tumour inhibition without noticeable tissue toxicity. Such EV-based delivery strategy, with a scalable EV loading approach, enhanced the in vivo PROTAC drug stability and bioavailability and improved tissue penetration and targeting, filling an important gap in the clinical translation of PROTAC-based cancer therapy.

In neurones, like in any other cell, their function often relies on the fine-tuning of their protein levels, which is achieved by the balance between protein synthesis and turnover. Defects in protein homeostasis frequently lead to neuronal dysfunction and neurological disorders. Given their extreme morphological complexity and high compartmentalization, neurones highly depend on the asymmetrical distribution of their proteome. The common belief is that proteins that sustain axonal, dendritic and synaptic functions are synthesized in the soma and then transported to distal neuronal compartments. However, there is a complementary mechanism by which the mRNAs, and not the proteins, are transported to distal subneuronal domains, and once they reach their destination, they are locally translated. Although once considered heretical, local translation (or local protein synthesis) is now widely accepted by the scientific community. Nonetheless, there is one question that remains largely unexplored in the field, and that is whether local translation in dendrites, axons and synapses is fully regulated by the neurone itself or if non-neuronal cells (e.g., glia) can modulate this mechanism in a non-cell-autonomous manner. Here, we combined primary neuronal cultures, astrocyte-derived extracellular vesicle (EVs) isolation, and proteomics to investigate whether astroglial EVs modulate local translation in axons. We show that EVs released by astrocytes exposed to amyloid-β peptide (Aβ) enhance protein synthesis specifically in distal axons and increase synaptic integrity. Proteomics analysis and western blotting identified the ribosomal protein Rps6 as an astroglial Aβ-EV cargo delivered to axons. Interestingly, genetic downregulation revealed the contribution of vesicular Rps6 to translation regulation in axons and synaptic integrity. To our knowledge, this is the first report that directly demonstrates glial control of local translation in neurones through EVs, revealing a novel glia-to-neurone communication mechanism in an experimental model of Alzheimer's disease (AD).

C1q is released by microglia, localizes on weak synapses and acts as a tag for microglial synaptic pruning. However, how C1q tags synapses during the pruning period remains to be fully elucidated. Here, we report that C1q is delivered via extracellular vesicles by microglia to pre-synaptic sites that externalize phosphatidylserine. Using approaches to increase or reduce vesicles production in microglia, by C9orf72 knock out or pharmacological inhibition, respectively, we provided mechanistic evidence linking extracellular vesicle release to pre-synaptic remodelling in neuron-microglia cultures. In C9orf72 knockout mice, we confirmed larger production of microglial extracellular vesicles and showed augmented C1q presynaptic deposition associated with enhanced engulfment by microglia in the early postnatal hippocampus. Finally, we provide evidence that microglia physiologically release more vesicles during the period of postnatal circuit refinement. These findings implicate abnormal release of microglial extracellular vesicles in both neurodevelopmental and age-related disorders characterized by dysregulated microglia-mediated synaptic pruning.

Extracellular vesicles (EVs) are an attractive delivery vehicle with biological activity, intrinsic homing, low immunogenicity, and engineerability; however, challenges remain regarding loading and functional delivery of mRNA. Here, we developed a novel approach to load mRNA through low pH-induced fusion of EVs with lipid nanoparticles (LNPs) to generate hybrid EVs (HEVs). Conventional characterization showed that HEVs preserved classical features of EVs. Single particle analysis revealed successful loading of mRNA and incorporation of LNP components into HEVs. The combined properties from EV and LNP contributed to the excellent cell tolerability of HEV, overcoming dose-limit toxicity, and functional delivery of mRNA by HEV. We further elucidated the mechanism of HEV-mediated intracellular delivery of mRNA. Our results showed that in contrast to source EVs, HEVs were capable of inducing endosomal escape, facilitating intracellular delivery of mRNA. Furthermore, HEVs functionally delivered mRNA in vivo and displayed extrahepatic delivery capacity with predominant functional distribution in spleen. Our results suggest HEVs as a promising EV-based delivery platform for mRNA delivery.

The concentration of cells is a key component of modern blood tests. Given the biomarker potential of extracellular vesicles (EVs) in blood, we aimed to establish reference ranges for blood cell-derived EVs using flow cytometry. To address the orders-of-magnitude variability in reported EV concentrations between different flow cytometers (FCMs), we first validated a calibration methodology to enable reproducible EV concentration measurements. The methodology was evaluated in an interlaboratory comparison study and shows that calibration reduces the median absolute deviation of EV concentrations measured on 25 different FCMs from 67 % to 25 %–31 %. The calibration methodology was then used to determine reference ranges of erythrocyte-, leukocyte-, and platelet-derived EVs in human blood plasma in a cohort of healthy individuals (n = 224). This study demonstrates that calibration enables comparable concentration measurements of blood cell-derived EVs, thereby bringing EVs one step closer to clinical applications.