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

Extracellular Vesicles in Cancer Biology

Extracellular vesicles (EVs) play a pivotal role in cancer biology, particularly in modulating immune responses and tumor progression. One significant study demonstrated that mitochondrial DNA (mtDNA) released by senescent tumor cells enhances the immunosuppressive activity of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) through the cGAS-STING pathway, indicating a mechanism by which senescent cells contribute to tumor immune evasion (ref: Lai doi.org/10.1016/j.immuni.2025.03.005/). In another investigation, the secretion of small EVs (sEVs) carrying microRNAs (miR-15-16) from endothelial cells was linked to cardiac damage in diabetic individuals, highlighting the systemic effects of EVs beyond the tumor microenvironment (ref: Ding doi.org/10.1016/j.cmet.2025.03.006/). Furthermore, research on CAR T cell therapy revealed that solid tumors can upregulate the secretion of tumor antigen-carrying EVs, which can lead to fratricide among CAR T cells, thus complicating treatment efficacy (ref: Zhong doi.org/10.1038/s43018-025-00949-8/). These findings collectively underscore the dual role of EVs in both promoting tumor growth and mediating immune responses, suggesting potential therapeutic targets for enhancing cancer treatments. The diagnostic potential of EV-derived small non-coding RNAs (sncRNAs) has also been explored, particularly in gastric cancer, where specific ribosomal RNA-derived and transfer RNA-derived small RNAs were identified as promising biomarkers (ref: Yang doi.org/10.1186/s13045-025-01689-z/). Additionally, the role of EVs in mediating immune responses was further emphasized by studies showing that engineered dendritic cell-derived EVs expressing interleukin-12 and anti-CTLA-4 can enhance T cell activation, indicating a novel approach for combinational cancer immunotherapy (ref: Chen doi.org/10.1002/jev2.70068/). Overall, the interplay between EVs and immune modulation presents a rich area for further investigation, particularly in the context of therapeutic interventions and biomarker discovery.

Extracellular Vesicles in Metabolic Disorders

The involvement of extracellular vesicles (EVs) in metabolic disorders has garnered attention, particularly regarding their role in mediating cardiovascular complications associated with diabetes. A pivotal study demonstrated that O-GlcNAcylation in endothelial cells leads to the continuous release of sEVs containing miR-15-16, which contributes to cardiac damage in diabetic individuals, emphasizing the long-term effects of metabolic dysregulation (ref: Ding doi.org/10.1016/j.cmet.2025.03.006/). Another study investigated the role of adipose tissue macrophages in metabolic dysfunction-associated steatohepatitis, revealing that EVs secreted by these macrophages activate liver fibrosis in obese male mice, thereby linking inflammation and metabolic dysregulation to liver pathology (ref: Rohm doi.org/10.1053/j.gastro.2025.03.033/). These findings highlight the critical role of EVs in mediating intercellular communication in metabolic disorders, suggesting that targeting EV pathways could offer therapeutic avenues. Moreover, weight loss in individuals with obesity and type 2 diabetes was shown to improve insulin sensitivity, accompanied by changes in circulating EV microRNAs, indicating a potential biomarker for monitoring metabolic health (ref: Samovski doi.org/10.2337/dc24-2739/). The integration of proteomic profiling in assessing diabetes risk further underscores the importance of EVs in understanding metabolic diseases, as demonstrated in a large-scale study that evaluated proteomic biomarkers alongside clinical risk scores (ref: Xie doi.org/10.2337/dc24-2478/). Collectively, these studies illustrate the multifaceted roles of EVs in metabolic disorders, from mediating cellular communication to serving as potential biomarkers for disease progression and therapeutic targets.

Extracellular Vesicles in Immune Response and Therapy

Extracellular vesicles (EVs) have emerged as crucial mediators in immune responses and therapeutic strategies, particularly in cancer immunotherapy. One study highlighted how solid tumors can exploit EVs to induce fratricide among CAR T cells, thereby limiting the efficacy of these therapies (ref: Zhong doi.org/10.1038/s43018-025-00949-8/). This finding underscores the need for innovative approaches to enhance CAR T cell therapy, such as engineering dendritic cell-derived EVs to express interleukin-12 and anti-CTLA-4, which can improve T cell activation and therapeutic outcomes (ref: Chen doi.org/10.1002/jev2.70068/). Additionally, the role of bacterial outer membrane vesicles engineered with tumor-targeting nanobodies was explored, demonstrating their potential to enhance antitumor immunity while minimizing toxicity (ref: Xia doi.org/10.1002/jev2.70069/). Moreover, the immunosuppressive effects of Fusobacterium nucleatum-derived EVs were shown to promote resistance to immunotherapy in head and neck squamous cell carcinoma, indicating that microbial-derived EVs can significantly impact tumor immune dynamics (ref: Li doi.org/10.1002/jev2.70070/). The characterization of EVs from pregnancies complicated by COVID-19 revealed their role in altering trophoblast function, suggesting that EVs can mediate immune responses in various physiological contexts (ref: Golden doi.org/10.1002/jev2.70051/). These studies collectively highlight the dual role of EVs in both promoting and inhibiting immune responses, emphasizing their potential as therapeutic targets and biomarkers in cancer treatment and beyond.

Extracellular Vesicles in Neurological Disorders

Research on extracellular vesicles (EVs) in neurological disorders has revealed their potential as biomarkers and mediators of disease progression. A significant study identified the presence of TDP-43, an RNA-binding protein associated with neurodegenerative diseases, in EVs, suggesting that these vesicles may facilitate intercellular communication in conditions like amyotrophic lateral sclerosis and frontotemporal dementia (ref: Corucci doi.org/10.1021/jacs.5c00594/). Furthermore, the aggregation of TDP-43 pathological fragments was shown to be driven by membrane charge, indicating that EVs could play a role in the pathophysiology of these disorders (ref: Kleefeld doi.org/10.1093/brain/). This highlights the importance of EVs in the context of neurodegeneration and their potential as therapeutic targets. Additionally, the diagnostic potential of EV-derived small non-coding RNAs (sncRNAs) was explored in gastric cancer, with findings suggesting that specific EV-derived RNAs could serve as novel biomarkers (ref: Yang doi.org/10.1186/s13045-025-01689-z/). The implications of EVs in metabolic dysfunction were also noted, particularly in the context of obesity and type 2 diabetes, where EVs from adipose tissue macrophages were shown to activate liver fibrosis (ref: Rohm doi.org/10.1053/j.gastro.2025.03.033/). These findings collectively underscore the multifaceted roles of EVs in neurological disorders, from serving as biomarkers to mediating disease mechanisms, warranting further investigation into their therapeutic applications.

Extracellular Vesicles in Regenerative Medicine

Extracellular vesicles (EVs) are gaining traction in regenerative medicine due to their ability to mediate tissue repair and regeneration. One study demonstrated that engineered EVs derived from juvenile mice could enhance mitochondrial function in the aging bone microenvironment, suggesting a potential strategy for rejuvenating aged tissues (ref: Zheng doi.org/10.1021/acsnano.4c17989/). This finding is particularly relevant in the context of age-related bone degeneration, where targeted delivery of EVs could restore bone health. Additionally, injectable EV hydrogels with tunable viscoelasticity were developed, providing a novel platform for depot vaccines and enhancing the retention of therapeutic EVs in tissues (ref: Bhatta doi.org/10.1038/s41467-025-59278-0/). Moreover, the use of glycoRNA detection methods on EVs has opened new avenues for cancer diagnostics, enabling sensitive profiling of glycoRNAs associated with various malignancies (ref: Ren doi.org/10.1038/s41467-025-58490-2/). These advancements highlight the versatility of EVs in both therapeutic and diagnostic applications, emphasizing their potential to revolutionize approaches in regenerative medicine. The integration of EVs into therapeutic strategies not only enhances the efficacy of treatments but also provides a platform for innovative diagnostic tools, paving the way for personalized medicine.

Biomarkers and Diagnostic Applications of Extracellular Vesicles

The exploration of extracellular vesicles (EVs) as biomarkers for disease diagnosis has gained momentum, particularly in cancer and metabolic disorders. One study focused on the use of the malaria protein VAR2CSA to detect cancer-derived small EVs, which could serve as early detection biomarkers for pancreatic ductal adenocarcinoma (ref: Zhao doi.org/10.1002/jev2.70067/). This innovative approach highlights the potential of EVs in providing sensitive and specific diagnostic tools for challenging cancers. Additionally, oscillating microbubble array-based metamaterials were developed for the rapid isolation of high-purity exosomes from biofluids, addressing a significant challenge in EV research and clinical applications (ref: Li doi.org/10.1126/sciadv.adu8915/). Furthermore, the characterization of EVs from pregnancies complicated by COVID-19 revealed their role in altering trophoblast function, suggesting that EVs can serve as biomarkers for monitoring pregnancy complications (ref: Golden doi.org/10.1002/jev2.70051/). The identification of non-canonical sncRNAs in plasma EVs as potential biomarkers for gastric cancer further emphasizes the diagnostic capabilities of EVs (ref: Yang doi.org/10.1186/s13045-025-01689-z/). Collectively, these studies underscore the promise of EVs in biomarker discovery and diagnostic applications, paving the way for improved disease detection and monitoring.

Technological Advances in Extracellular Vesicle Research

Recent technological advancements in the field of extracellular vesicle (EV) research have significantly enhanced the ability to isolate and characterize these important biological entities. One notable development is the implementation of high-throughput size exclusion chromatography (SEC) using plate-based systems, which allows for the efficient isolation of EVs from various biofluids, thereby facilitating large-scale studies (ref: Gilboa doi.org/10.1021/jacs.4c17948/). This method not only improves the yield of isolated EVs but also streamlines the process, making it more accessible for researchers. Additionally, the use of oscillating microbubble array-based metamaterials has emerged as a novel approach for the rapid isolation of high-purity exosomes, addressing the challenges of traditional isolation techniques (ref: Li doi.org/10.1126/sciadv.adu8915/). Moreover, advancements in detection methods, such as dual recognition Förster resonance energy transfer (drFRET), have enabled sensitive profiling of glycoRNAs on EVs, which could enhance cancer diagnostics (ref: Ren doi.org/10.1038/s41467-025-58490-2/). These technological innovations not only improve the efficiency of EV research but also expand the potential applications of EVs in diagnostics and therapeutics. As the field continues to evolve, these advancements will likely lead to more refined methodologies for studying EVs, ultimately enhancing our understanding of their roles in health and disease.

Key Highlights

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