Research on extracellular vesicles including exosomes, microvesicles, and their roles in intercellular communication and disease

Extracellular Vesicles in Disease Mechanisms

Extracellular vesicles (EVs) play a pivotal role in various disease mechanisms, particularly in autoimmune and chronic diseases. For instance, a study demonstrated that mesenchymal stromal cells (MSCs) induce a significant increase in neutrophil aggregation and the release of EVs in systemic lupus erythematosus (SLE). The blockade of this EV storm was shown to abolish the therapeutic effects of MSCs, indicating that the EV storm can serve as a predictive marker for therapeutic efficacy in SLE patients (ref: Ou doi.org/10.1038/s41392-025-02442-1/). Similarly, in rheumatoid arthritis, engineered apoptotic EVs were developed to regulate the pathogenic axis involving neutrophils and macrophages, showcasing a novel approach to reconstruct the rheumatoid arthritis microenvironment and improve therapeutic outcomes (ref: Kang doi.org/10.1002/adma.202508072/). Furthermore, hepatocyte-derived EVs were found to promote endothelial dedifferentiation in chronic liver disease through specific miRNA pathways, highlighting the complex interplay between EVs and disease progression (ref: Abad-Jordà doi.org/10.1097/HEP.0000000000001567/). These studies collectively emphasize the multifaceted roles of EVs in mediating disease mechanisms and their potential as therapeutic targets or biomarkers. In cancer research, engineered dendritic cell progenitors expressing EV-internalizing receptors significantly enhanced cancer immunotherapy efficacy in mouse models. This approach facilitates the internalization of tumor-derived antigens, thereby improving the immune response against tumors (ref: Ghasemi doi.org/10.1038/s41467-025-64172-w/). Additionally, engineered neural stem cell-derived EVs activating Wnt signaling were shown to promote blood-brain barrier repair after cerebral hemorrhage, indicating their therapeutic potential in neurological disorders (ref: Li doi.org/10.1093/brain/). The heterogeneity of EVs, particularly in glioblastoma, was also explored, revealing distinct lipid and protein signatures that correlate with tumor characteristics, thus providing insights into their roles in cancer biology (ref: Xu doi.org/10.1002/jev2.70168/). Overall, the research underscores the diverse functions of EVs in disease mechanisms, suggesting their utility in diagnostics and therapy.

Extracellular Vesicles in Cancer Therapy

The application of extracellular vesicles (EVs) in cancer therapy has gained significant attention due to their ability to modulate immune responses and deliver therapeutic agents. One study identified a novel mechanism termed the 'FOotprint Of Death' (FOOD), where apoptotic cells leave behind a membrane-encased footprint that signals to phagocytic cells, potentially enhancing the clearance of dead cells and influencing immune responses (ref: Rutter doi.org/10.1038/s41467-025-64206-3/). Additionally, Munc13-4 was shown to regulate the sorting and secretion of PD-L1 via exosomes, with its deletion enhancing T cell-mediated anti-tumor immunity and improving the efficacy of immune checkpoint inhibitors (ref: Liu doi.org/10.1038/s41467-025-64149-9/). This highlights the potential of targeting exosomal pathways to enhance cancer immunotherapy. Moreover, engineered exosomes carrying WNT and R-spondin proteins were developed to synergistically activate WNT signaling, promoting liver repair and regeneration, which could have implications for treating liver cancers (ref: Yang doi.org/10.1038/s41467-025-64069-8/). The discovery of sex-specific dysregulation of exosomal non-coding RNAs in multiple myeloma further emphasizes the need for personalized therapeutic approaches based on molecular profiles (ref: Maleknia doi.org/10.1038/s41408-025-01362-1/). Collectively, these findings illustrate the diverse roles of EVs in cancer therapy, from enhancing immune responses to delivering therapeutic agents, and underscore the importance of further research in this area.

Extracellular Vesicles in Regenerative Medicine

Extracellular vesicles (EVs) are emerging as promising tools in regenerative medicine due to their ability to facilitate tissue repair and regeneration. A notable study developed magnetically labeled induced pluripotent stem cell-derived EVs (magneto-iPSC-EVs) for MRI/MPI-guided regenerative therapy in myocardial infarction. These EVs were characterized according to MISEV2023 guidelines and demonstrated high loading efficiency of superparamagnetic iron oxide nanoparticles, allowing for precise tracking and targeted therapy (ref: Wang doi.org/10.1002/jev2.70178/). This innovative approach highlights the potential of EVs in enhancing the efficacy of regenerative therapies. Furthermore, a novel strategy for acquiring metabolically-tagged nascent EVs was introduced, which could aid in identifying surface protein markers from neuroblastoma cells cultured with native serum. This method addresses the challenges of isolating tumor-derived EVs and could improve the specificity of liquid biopsy techniques (ref: Markus doi.org/10.1002/jev2.70177/). Additionally, the impact of 3D nanofibrillar matrix stiffness on EV cargo and pro-tumor functions was investigated, revealing that the mechanical properties of the extracellular matrix can significantly influence EV behavior and their therapeutic potential (ref: Wang doi.org/10.1002/jev2.70165/). These studies collectively underscore the versatility of EVs in regenerative medicine, paving the way for novel therapeutic strategies.

Extracellular Vesicles in Immune Response

Extracellular vesicles (EVs) play a crucial role in modulating immune responses, particularly in the context of cancer and infectious diseases. Engineered dendritic cell progenitors expressing extracellular-vesicle-internalizing receptors have been shown to enhance cancer immunotherapy by promoting the internalization of tumor-derived antigens, thereby improving the immune response against tumors (ref: Ghasemi doi.org/10.1038/s41467-025-64172-w/). This innovative approach highlights the potential of EVs in enhancing the efficacy of immunotherapeutic strategies. In the context of neurological disorders, engineered neural stem cell-derived EVs activating Wnt signaling were found to promote blood-brain barrier repair after cerebral hemorrhage, suggesting their therapeutic potential in restoring immune homeostasis in the central nervous system (ref: Li doi.org/10.1093/brain/). Additionally, the study of vesicle adaptors in malaria parasites revealed insights into the conservation and flexibility of protein sorting machinery, which is critical for effective immune responses during infection (ref: Cubillán-Marín doi.org/10.1083/jcb.202504062/). These findings collectively emphasize the diverse roles of EVs in regulating immune responses, offering new avenues for therapeutic interventions.

Extracellular Vesicles in Metabolic Disorders

Extracellular vesicles (EVs) have emerged as significant players in the pathophysiology of metabolic disorders, particularly type 2 diabetes (T2D). A study demonstrated that D-mannose can alleviate T2D and associated multi-organ deteriorations by controlling the release of pathological EVs, highlighting the potential of targeting EVs in metabolic disease management (ref: Zhang doi.org/10.1002/EXP.20240133/). This finding underscores the importance of EVs as mediators of intercellular communication in metabolic dysregulation. Moreover, the characterization of EVs derived from different adipose tissue macrophages revealed functional differences in their impact on insulin sensitivity, with subcutaneous adipose tissue macrophages releasing small EVs that improve insulin sensitivity, contrasting with the effects of visceral adipose tissue macrophages (ref: Jeelani doi.org/10.1016/j.celrep.2025.116450/). This suggests that the origin of EVs can significantly influence their biological effects in metabolic contexts. Additionally, the study of EVs in the context of prostate cancer highlighted their potential as biomarkers for distinguishing molecular subtypes, further emphasizing their relevance in metabolic and cancer-related disorders (ref: Ludwig doi.org/10.1002/jev2.70176/). Collectively, these studies illustrate the multifaceted roles of EVs in metabolic disorders and their potential as therapeutic targets.

Extracellular Vesicles in Neurological Disorders

Extracellular vesicles (EVs) are increasingly recognized for their roles in neurological disorders, particularly in mediating communication and repair mechanisms in the central nervous system. A significant study demonstrated that engineered neural stem cell-derived EVs, when loaded with a Wnt-tropic ligand, promote blood-brain barrier repair after cerebral hemorrhage, indicating their therapeutic potential in neurological injuries (ref: Li doi.org/10.1093/brain/). This finding highlights the capacity of EVs to facilitate recovery processes in the brain. In addition, the engineering of dendritic cell progenitors to express EV-internalizing receptors has shown promise in enhancing cancer immunotherapy, suggesting that EVs can also play a role in modulating immune responses within the neurological context (ref: Ghasemi doi.org/10.1038/s41467-025-64172-w/). Furthermore, the study of vesicle adaptors in malaria parasites provided insights into the protein sorting machinery that is crucial for effective immune responses, which may have implications for understanding similar mechanisms in neurological disorders (ref: Cubillán-Marín doi.org/10.1083/jcb.202504062/). These studies collectively underscore the diverse functions of EVs in neurological disorders, paving the way for innovative therapeutic strategies.

Extracellular Vesicles in Cardiovascular Diseases

Extracellular vesicles (EVs) are gaining recognition for their roles in cardiovascular diseases, particularly in regenerative therapies. A study developed magnetically labeled induced pluripotent stem cell-derived EVs (magneto-iPSC-EVs) for MRI/MPI-guided regenerative treatment of myocardial infarction, demonstrating their potential for targeted therapy and real-time tracking (ref: Wang doi.org/10.1002/jev2.70178/). This innovative approach highlights the utility of EVs in enhancing the precision of cardiovascular interventions. Additionally, the characterization of EVs derived from different adipose tissue macrophages revealed significant differences in their roles in insulin sensitivity, with small EVs from subcutaneous adipose tissue macrophages improving insulin sensitivity, contrasting with the effects of visceral adipose tissue macrophages (ref: Jeelani doi.org/10.1016/j.celrep.2025.116450/). This finding emphasizes the importance of EV origin in determining their biological effects in cardiovascular contexts. Furthermore, the study of 3D nanofibrillar matrix stiffness on EV cargo and pro-tumor functions provided insights into how the extracellular matrix can influence EV behavior, which is critical for understanding their roles in cardiovascular diseases (ref: Wang doi.org/10.1002/jev2.70165/). Collectively, these findings illustrate the multifaceted roles of EVs in cardiovascular diseases and their potential as therapeutic agents.

Extracellular Vesicles in Biomarker Discovery

Extracellular vesicles (EVs) are emerging as valuable sources for biomarker discovery, particularly in cancer diagnostics. A study introduced a novel strategy for acquiring metabolically-tagged nascent EVs, which can facilitate the identification of surface protein markers from neuroblastoma cells cultured with native serum. This method addresses the challenges of isolating tumor-derived EVs and could enhance the specificity of liquid biopsy techniques (ref: Markus doi.org/10.1002/jev2.70177/). This advancement underscores the potential of EVs in non-invasive cancer diagnostics. Moreover, the proteomic profiling of EVs has been shown to distinguish molecular subtypes of prostate cancer, revealing significant differences in cargo that could serve as biomarkers for disease stratification (ref: Ludwig doi.org/10.1002/jev2.70176/). Additionally, the development of signal amplification strategies for fluorescent staining of single EVs has improved the detection of low-abundance markers, further enhancing the utility of EVs in biomarker discovery (ref: Cavallaro doi.org/10.1002/jev2.70167/). These studies collectively highlight the significant potential of EVs as biomarkers in cancer and other diseases, paving the way for innovative diagnostic approaches.

Key Highlights

  • The blockade of the EV storm abolishes the MSC-mediated therapeutic effect for SLE, indicating its predictive value (ref: Ou doi.org/10.1038/s41392-025-02442-1/)
  • Engineered apoptotic EVs regulate the neutrophil-macrophage-ROS pathogenic axis in rheumatoid arthritis, showcasing a novel therapeutic approach (ref: Kang doi.org/10.1002/adma.202508072/)
  • Magnetically labeled iPSC-derived EVs enable MRI/MPI-guided regenerative therapy for myocardial infarction, demonstrating their potential in cardiovascular applications (ref: Wang doi.org/10.1002/jev2.70178/)
  • D-mannose alleviates type 2 diabetes by controlling the release of pathological EVs, highlighting a novel therapeutic target (ref: Zhang doi.org/10.1002/EXP.20240133/)
  • The 'FOotprint Of Death' mechanism enhances immune signaling at the site of cell death, potentially improving cancer immunotherapy (ref: Rutter doi.org/10.1038/s41467-025-64206-3/)
  • Sex-specific dysregulation of exosomal non-coding RNAs drives multiple myeloma progression, emphasizing the need for personalized therapies (ref: Maleknia doi.org/10.1038/s41408-025-01362-1/)
  • Proteomic profiling of EVs distinguishes prostate cancer molecular subtypes, offering insights for targeted diagnostics (ref: Ludwig doi.org/10.1002/jev2.70176/)
  • Signal amplification strategies enhance the detection of single EVs, improving the specificity of liquid biopsies (ref: Cavallaro doi.org/10.1002/jev2.70167/)

Disclaimer: This is an AI-generated summarization. Please refer to the cited articles before making any clinical or scientific decisions.