Extracellular vesicles and circulating nucleic acids最新文献

Extracellular vesicles (EVs) are a type of cell-released phospholipid bilayer nanoscale carrier. However, research on EVs encounters several challenges, such as their heterogeneity, the complexities associated with their isolation and identification, the necessity for engineering optimization, and the limitations in exploring their mechanisms. The advancement of artificial intelligence (AI) technologies offers new opportunities for EV research. Here, the definition and brief history of AI, as well as types and common models of machine learning, are first introduced, and the interactions between AI, machine learning, and deep learning are explored. The article then discusses in detail a variety of applications of AI in EV research, including the use of AI for target identification and selective delivery of EVs, the design and optimization of drug delivery systems, the mapping of cellular communication networks, the analysis of multi-omics data, and synthetic biology-based research on EVs. These applications demonstrate the potential of AI in advancing EV research and applications. Finally, we offer an outlook on the major challenges and future prospects of AI. Overall, the introduction of AI technologies has provided new perspectives and tools for the study of EVs, which is expected to enhance the application of EVs in disease diagnosis and treatment.

In December 2024, the United Kingdom Society for Extracellular Vesicles (UKEV) held its annual forum in Newcastle upon Tyne, marking 11 years since its founding. UKEV Forum 2024 brought together over 230 participants from the UK and abroad under the theme "Bridging Innovation and Impact". The meeting emphasised translational science, regulatory foresight, methodological rigour, and cross-sector collaboration, reflecting the maturation of EV research towards clinical relevance. Hosted at Newcastle University, the event included plenary lectures, oral and lightning talks, poster sessions, and an Early Career Researcher (ECR) Day. Scientific discussions spanned EV biomarker discovery, mechanistic studies, tissue-derived EVs, and novel analytical tools such as cryo-TEM, electrochemical sensors, and DNA-PAINT microscopy. The forum showcased emerging topics in EV isolation, reproducibility, therapeutic development, and regulatory integration, drawing on diverse expertise across academia, biotech, and clinical sciences. Generous industry sponsorship and inclusive programming made UKEV 2024 a landmark event that reinforced the UK's leadership in EV research.

The GISM Annual Meeting 2025 convened experts in regenerative medicine and nanomedicine to discuss recent advances in mesenchymal stromal/stem cell (MSC) research and extracellular vesicle (EV) technologies. The meeting emphasized novel strategies to enhance the therapeutic potential of MSCs and EVs, addressing both basic biological insights and translational challenges. Discussions highlighted the importance of standardizing production and characterization methods to improve scalability and reproducibility for clinical applications. Emerging therapeutic approaches, including cell engineering and targeted drug delivery, were showcased alongside preclinical and clinical studies. The conference provided a platform for interdisciplinary exchange, fostering collaboration and paving the way toward the clinical integration of EV and cell-based nanomedicine.

Exosomes, as key mediators of intercellular communication, have shown great potential in disease intervention and therapy in recent years. As natural nanocarriers, exosomes play a crucial role in transporting a wide array of cargo. Among these, miRNAs carried by exosomes are pivotal in gene regulation and the modulation of cellular signaling. Given that miRNAs are essential gene regulators, understanding how miRNAs are selectively loaded into exosomes is crucial for the development of novel diagnostic and therapeutic approaches. This review provides a detailed overview of the biogenesis and secretion mechanisms of exosomes, with a particular focus on the molecular mechanisms governing miRNA sorting into exosomes. Specifically, it highlights the miRNA motifs associated with exosomes enrichment (EXOmotifs), as well as those related to intracellular miRNA enrichment (CELLmotifs), along with RNA-binding proteins (RBPs) involved in sorting. We summarize the current progress in this field and discuss strategies for engineering Exosomes - such as gene editing, drug loading, and surface modification - to enhance their functionality and specificity. By exploring these mechanisms, this review offers a theoretical foundation for the application of engineered exosomes in disease treatment and outlines future research directions and potential applications.

Aim: Extracellular vesicles (EVs) have emerged as promising vehicles for the delivery of small non-coding RNAs (sncRNAs); however, their clinical translation is hindered by the lack of standardized manufacturing methods, RNA loading protocols, and dosing strategies in both preclinical and clinical settings. This review aims to analyze the current landscape of EV-based RNA therapeutics to identify key trends and discrepancies, providing insight for the clinical development of future sncRNA-loaded EVs. Methods: PubMed and Google Scholar were used to identify 74 published articles using cell-derived EVs loaded with sncRNA. EV source, EV surface modifications, type of loaded RNA, loading methods, and dosages used in preclinical studies were quantitatively analyzed to identify trends and discrepancies. Results: Most studies utilize naïve EVs derived from stem or immortalized cells, with electroporation and donor cell transfection being the predominant RNA loading strategies. EV loading and dosage schemes in preclinical studies are mainly based on protein content, while only a minority of studies use particle number. More generally, the variability in measurement units reflects the absence of standardized guidelines for both RNA loading and treatment dosing, generating variability and challenges in comparing results across studies. Conclusion: Reliable dosing strategies are extremely important for determining the therapeutic potential of EVs in preclinical settings and ensuring clinical translatability. However, a standardized framework for EVs as robust platforms for RNA delivery remains to be established. We underscore the critical need for universal quantification methods, standardized measurement units, and reproducible protocols for EV production and application.

Aim: Gram-negative bacteria release outer membrane vesicles (OMVs) that fulfill many functions including survival during stress conditions, delivery of virulence factors, and nutrient acquisition. Additionally, they are increasingly used as an alternative for live bacteria in vaccine development and as a platform for bioengineering. Recently, OMVs have also been applied to express recombinant outer membrane proteins (OMPs) in their natural context as an alternative to the cumbersome reconstitution in liposomes. Here, we use an Escherichia coli strain that lacks four major OMPs for selective expression of the β-barrel assembly machinery (BAM) complex and PhoE in OMVs. Methods: OMV production of Escherichia coli BL21(DE3) and its omp8 derivative upon overexpression of BAM and PhoE is compared and characterized. Results: We find that overexpression of the BAM complex and PhoE causes a strong hypervesiculation phenotype, and the OMVs produced are intact and appear to recruit the BamA subunit of BAM and PhoE in their correctly folded and assembled conformations. Conclusion: While the exact mechanism of hypervesiculation remains to be elucidated, it contributes to the suitability of the BL21(DE3)omp8 host strain to produce recombinant OMP-enriched OMVs that can be used for various purposes, including structural analysis.

Extracellular vesicles (EVs) are secreted by nearly all cell types and fulfil a crucial role in intercellular communication by transporting diverse cargo, including enzymes, mRNA, growth factors, chemokines, and cytokines. Although EVs were initially thought to primarily function in waste elimination, it is now clear that they can be diverted from degradation and instead actively secreted to mediate intercellular communication. While the processes of EV biogenesis, degradation, and release have been extensively studied, many aspects remain poorly understood. The involvement of molecular pathways shared by EV biogenesis and autophagy - a lysosome-mediated disposal mechanism - suggests the existence of common regulatory controls. Despite the partial overlap in molecular machineries involved in cargo sorting, the mechanisms that balance the degradation and secretory pathways of EVs, as well as their interplay with autophagy, remain elusive. This review discusses the molecular machinery that dictates the selective cargo loading into EVs. Additionally, it examines the coordination between degradation and secretory pathways in EV biology and situates these processes within the broader context of autophagy. The substantial overlap in molecular pathways, shared proteins, and complementary mechanisms suggests a high degree of coordination between these systems.

Blebbisomes represent a newly identified class of large extracellular vesicles (EVs) that exhibit unique functional capabilities in intercellular communication. Beyond their motility, blebbisomes engage in complex vesicle trafficking functions. Strikingly, they are capable of both internalizing and secreting other EVs, essentially acting as intermediaries or "hubs" in intercellular communication networks.

In a recent study, Antounians and colleagues (2024) investigated the potential of amniotic fluid stem cell-derived extracellular vesicles (AFSC-EVs) as a therapeutic intervention for pulmonary hypoplasia resulting from congenital diaphragmatic hernia (CDH). They demonstrated the pronounced inflammatory signature of the fetal hypoplastic lungs, marked by heightened macrophage density in a CDH rat model. Intra-amniotic AFSC-EV administration mitigated the inflammatory process and enhanced fetal lung development by promoting branching morphogenesis and epithelial maturation. These findings add to a growing body of preclinical and clinical evidence supporting the therapeutic potential of AFSC-EVs for inflammation-driven pathologies.