The intertwined nature of cardiac and renal failure, where dysfunction in one organ predicts a poor outcome in the other, has long driven the interest in uncovering the exact molecular links between the two. Elucidating the mechanisms driving Cardiorenal Syndrome (CRS) will enable the development of targeted therapies that disrupt this detrimental cycle, potentially improving outcomes for patients. A recent study by Chatterjee et al. (JCI insight 2023) demonstrated the feasibility of utilizing a humanized microfluidic kidney-on-chip model to elucidate the role of circulating extracellular vesicles (EVs) in the development of CRS (type 1 and type 2) in heart failure (HF) patients. The study also identified and validated EV miRNAs that correlated with kidney function by targeting several genes involved in kidney damage pathways, including transforming growth factor- β (TGF-β) signaling. These findings suggest that plasma EVs from CRS patients induce harmful responses in renal cells by regulating key pathways, highlighting their role in both type 1 and type 2 CRS.

Aim: Extracellular vesicles (EVs) are involved in intercellular and interkingdom communication in the complex communities that constitute the niche-specific microbiome of the colonized host. Therefore, studying the structure and content of EVs produced by resident bacteria is crucial to understanding their functionality and impact on the host and other microorganisms.

Methods: Bacterial EVs were isolated by differential centrifugation, their size and concentration were measured by transmission electron microscopy and nanoparticle tracking analysis, and the cargo proteins were identified by liquid chromatography coupled to tandem mass spectrometry. The cytotoxicity of bacterial EVs was tested using the human epithelial cell line A549 and an in vivo model of Galleria mellonella larvae.

Results: The isolation and preliminary characteristics of EVs from two strains of lactic acid bacteria - Lactiplantibacillus plantarum PCM 2675 and Lacticaseibacillus rhamnosus PCM 489 - were presented, confirming the production of vesicular structures with sizes in the range of 50-170 nm for L. plantarum and 80-250 nm for L. rhamnosus. In addition, various proteins were identified within EVs cargo, with distinct locations of origin, including membrane, cytoplasmic and extracellular proteins, and with diverse functions, including enzymes with confirmed proteolytic activity. Furthermore, bacterial EVs did not show statistically significant cytotoxicity to the host under the tested conditions.

Conclusions: A better understanding of the composition and functionality of bacterial EVs may contribute to their future effective use in supporting human health.

Aim: The article explores celery-derived extracellular vesicles (CDEVs), characterized by high cellular uptake, low immunogenicity, and high stability, as a therapeutic strategy for antitumor nanomedicines.

Methods: The methods employed in this study include in vitro cell experiments such as co-culture, Western Blot, and flow cytometry. In vivo experiments were conducted in C57BL/6 tumor-bearing mice subcutaneously injected with Lewis lung carcinoma (LLC) cells. The experiments encompassed parameters such as survival rate, body weight, tumor size, flow cytometry, immunohistochemistry, and spectral live imaging system.

Results: Our study revealed that CDEVs could be used as drugs to effectively downregulate the phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/programmed cell death ligand 1 (PD-L1) axis in lung cancer cells. In co-culture experiments, CDEVs were observed to impede the expression of PD-L1, thereby interfering with the interaction between PD-L1 and programmed death 1 (PD-1) and subsequently preventing the suppression of T cells. In in vivo distribution experiments, CDEVs loaded with paclitaxel (PTX) demonstrated better tumor targeting capabilities. Remarkably, following CDEVs-PTX treatment, CD8+ T cell levels in mice were increased, presumably leading to improved antitumor effects.

Conclusion: CDEVs not only serve as drug carriers but also function as drugs themselves; as such, through a single administration of CDEVs, it is possible to combine immunotherapy and chemotherapy to achieve better effects between the two, providing a more comprehensive and effective cancer treatment strategy that promises to improve treatment outcomes and reduce the adverse effects of therapy.

The recent study from the Pogge von Strandmann group published in Cellular and Molecular Immunology, by Alashkar Alhamwe et al., combined for the first time the Cre-LoxP recombination system with single-cell sequencing. The group monitored the tumor-derived extracellular vesicle (EV) uptake and the EV functions in the recipient non-malignant cells in a pancreatic ductal adenocarcinoma mouse model. Recombination events and EV uptake, together with resulting gene expression changes in macrophages, neutrophils, and mast cells, were detected by single-cell sequencing technology of the tumor tissue. This new approach is highly specific, as it can identify single EV recipient cells without interfering with the EV biogenesis or the phenotype.

Recent findings have indicated that the deficiency of inhibitory programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9) in pancreatic β-cells is associated with the progression of type 1 diabetes (T1D). This suggests that exogenous PD-L1 and Gal-9 may have promising potential as therapeutics for the treatment of T1D. In light of these reports, a recent work investigated the potential of artificial extracellular vesicles (aEVs) with the presentation of PD-L1 and Gal-9 ligands (PD-L1–Gal-9 aEVs) as a treatment for T1D, with the findings published in Diabetes. Notably, the PD-L1–Gal-9 aEVs demonstrated the capacity to induce apoptosis of T cells and the formation of regulatory T (Treg) cells, thereby maintaining immune tolerance. Furthermore, the in vivo administration of PD-L1–Gal-9 aEVs resulted in a reduction in T cell infiltration in the pancreas, an increase in β-cell integrity protection, a significant decrease in blood glucose levels, and a delay in the progression of T1D. In conclusion, this study proposed an innovative approach to the treatment of T1D progression through the use of immunosuppressive EVs. This highlight provides a comprehensive analysis and discussion of the pivotal findings of this study.

Mesenchymal stromal cells (MSCs) showed promising potential for regenerative and therapeutic applications for several pathologies and conditions. Their potential is mainly ascribed to the factors and extracellular vesicles (EVs) they release, which are now envisioned as cell-free therapeutics in cutting-edge clinical studies. A main cornerstone is the preferential uptake by target cells and tissues, in contrast to clearance by phagocytic cells or removal from circulation before reaching the final destination. Recent literature has suggested how the surface properties of EVs might influence their half-life, bio-distribution, and specific uptake. In particular, the concept of a protein corona surrounding EVs emerged. Especially for culture-purified EVs, the process of tailoring a treatment or tissue-specific corona was explored. Liam-Or et al. examined the impact of protein corona on MSC-EVs when specific proteins, preferentially albumin, were adsorbed from media on the EV surface before isolation. This resulted in improved uptake by liver parenchymal cells and reduced incorporation by macrophages, together with an increased half-life in the circulation system. Thus, producing MSC-EVs with an albumin-enriched protein corona might be a camouflage strategy to enhance non-phagocytic uptake in the liver. This research might be a milestone for future studies on other EVs-camouflage approaches tailored to specific tissues and therapeutic applications.

This report summarizes the ASEV-CzeSEV Joint Meeting on Extracellular Vesicles (EVs), held at the Medical University of Vienna in September 2024. The conference focused on introducing and expanding EV research and infrastructure within the Czech Republic and Austria, highlighting areas for collaboration. Key sessions featured research on EV-based diagnostics, tissue regeneration, interspecies communication and therapeutic applications, with an emphasis on shared resources and cross-border partnerships. The program included oral and poster presentations on EV engineering, new isolation techniques, and potential clinical applications, as well as industry updates on the latest EV technologies. The meeting concluded with awards for outstanding presentations reflecting the quality of work presented. Following the conference, a dedicated workshop was held on flow cytometry analysis of EVs, allowing participants to deepen their technical expertise in EV characterization. This report captures the main discussions, findings, and collaborative opportunities explored at the ASEV-CzeSEV meeting, signaling strong regional support for advancing EV research.

The effective management of cancer pain continues to be a challenge because of our limited understanding of cancer pain mechanisms and, in particular, how cancer cells interact with neurons to produce pain. In a study published in Pain, Inyang et al. used a mouse model of human papillomavirus (HPV1)-induced oropharyngeal squamous cell carcinoma to show a role for cancer cell-derived extracellular vesicles (cancer sEVs) in cancer pain. They found that inhibiting the release of sEVs reduced spontaneous and evoked pain behaviors, and that pain produced by sEVs is due to activation of TRPV1 channels. An innovative approach was the use of publicly available human RNA-sequencing data from unstimulated cultured human dorsal root ganglia (DRG) that were exposed to human head and neck squamous cell carcinoma (HNSCC)-derived sEVs to identify signaling pathways involved in the nascent translation associated with nociception. These studies further our understanding of functional interactions between cancer cells and neurons, and suggest an approach to identify novel targets for the treatment of cancer pain.

Current approaches to oral cancer diagnosis primarily involve physical examination, tissue biopsy, and advanced computer-aided imaging techniques. However, despite these advances, patient survival rates have not significantly improved. Hence, there is a critical need to develop minimally invasive tools with high sensitivity and specificity to improve patient survival and quality of life. Liquid biopsy is a non-invasive, real-time method for predicting cancer status and potentially serves as a biomarker source for treatment response. Liquid biopsy includes rich biologically relevant components, such as circulating tumor cells, circulating tumor DNA, and extracellular vesicles (EVs). EVs are particularly intriguing due to their relatively high abundance in most biofluids, with the potential to identify specific cargo derived from circulating tumor EVs. Moreover, normal cells in lymph nodes can uptake EVs, fostering a pre-metastatic microenvironment that facilitates lymph node metastases - a common occurrence in oral cancers.

This review encompasses English language publications over the last twenty years, focusing on methods for isolating EVs from saliva, blood, and lymphatic fluids, as well as the collection methods employed. Seventeen cases met the inclusion criteria according to ISEV guidelines, including 10 saliva cases, 6 blood cases, and 1 lymphatic fluid case. This review also highlighted research gaps in oral squamous cell carcinoma (OSCC) EVs, including a lack of multi-omics studies and the exploration of potential EV markers for drug resistance, as well as a notable underutilization of microfluidic technologies to translate liquid biopsy EV findings into clinical applications.