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 the context of tumor progression and metastasis. One study highlights how tumor-derived arachidonic acid reprograms neutrophils, promoting immune suppression and therapy resistance in triple-negative breast cancer (TNBC). This research indicates that TNBC cells surviving anti-PD-1 and chemotherapy treatments accumulate neutral lipids, suggesting a mechanism of acquired resistance (ref: Yu doi.org/10.1016/j.immuni.2025.03.002/). Another significant finding is the role of small extracellular vesicles (sEVs) derived from tumor-free pre-metastatic organs, which were shown to promote breast cancer metastasis and support organotropism, indicating that even non-tumor tissues can influence cancer progression (ref: Cheytan doi.org/10.1186/s12943-025-02235-8/). Additionally, a multi-phase study identified blood-derived exosomal tumor RNA signatures as non-invasive diagnostic biomarkers for multiple cancers, emphasizing the potential of EVs in early cancer detection (ref: Wang doi.org/10.1186/s12943-025-02271-4/). These findings collectively underscore the complex interplay between EVs and cancer biology, revealing both diagnostic and therapeutic implications. The methodology employed across these studies varies, with some utilizing RNA sequencing and single-cell data integration to identify biomarkers, while others focus on the functional roles of sEVs in immune modulation and tumor microenvironment interactions. For instance, the study on limb ischemic conditioning demonstrated that muscle-to-liver transfer of sEVs and their microRNA cargo could alleviate steatohepatitis, showcasing how EVs can mediate beneficial effects beyond cancer (ref: Zhao doi.org/10.1016/j.cmet.2025.02.009/). Furthermore, the programmable production of bioactive EVs via a bioelectronic interface presents a novel approach to localized treatment of myocardial infarction, indicating the versatility of EV applications in regenerative medicine as well (ref: Fu doi.org/10.1038/s41467-025-58260-0/).

Extracellular Vesicles in Cardiovascular Health

The role of extracellular vesicles (EVs) in cardiovascular health has gained significant attention, particularly in understanding their implications in conditions such as myocardial infarction and steatohepatitis. One study demonstrated that remote limb ischemic conditioning alleviates metabolic dysfunction-associated steatohepatitis through muscle-to-liver transfer of small extracellular vesicles (sEVs), which elevate hepatic miR-181d-5p levels and suppress nuclear receptor 4A3 (ref: Zhao doi.org/10.1016/j.cmet.2025.02.009/). This highlights the potential of sEVs as mediators of inter-organ communication and their therapeutic implications in liver diseases. Additionally, research into podoplanin-positive cell-derived sEVs has revealed their contribution to cardiac amyloidosis following myocardial infarction, indicating that EVs can also play a role in post-injury complications (ref: Cimini doi.org/10.1016/j.celrep.2025.115408/). Moreover, the development of programmable bioactive EVs for localized treatment of myocardial infarction represents a significant advancement in cardiovascular therapies. This approach utilizes a bioelectronic interface to stimulate macrophages for on-demand EV production, showcasing the innovative applications of EVs in regenerative medicine (ref: Fu doi.org/10.1038/s41467-025-58260-0/). The integration of these findings emphasizes the dual role of EVs in both promoting health and contributing to disease processes, thereby presenting new avenues for therapeutic interventions in cardiovascular health.

Extracellular Vesicles in Neurological Disorders

Extracellular vesicles (EVs) have emerged as crucial players in the context of neurological disorders, particularly in Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). A pivotal study demonstrated that plasma p-tau217 and tau-PET imaging are strong prognostic biomarkers for cognitive decline in cognitively unimpaired individuals, suggesting that these biomarkers could be instrumental in early detection and intervention strategies for AD (ref: Ossenkoppele doi.org/10.1038/s43587-025-00835-z/). This highlights the potential of EVs in carrying critical biomarkers that reflect underlying pathological processes in neurodegenerative diseases. In ALS, elevated levels of phosphorylated tau (p-tau) in serum and muscle biopsies were identified, indicating a possible link between tau pathology and muscle degeneration (ref: Abu-Rumeileh doi.org/10.1038/s41467-025-57144-7/). Furthermore, the analysis of urinary EVs in myotonic dystrophy type 1 revealed disordered renal metabolism, suggesting that EVs can provide insights into systemic metabolic changes associated with neurological disorders (ref: Kumari doi.org/10.1038/s41467-025-56479-5/). These findings collectively underscore the significance of EVs as both biomarkers and mediators of disease processes in neurological conditions, paving the way for novel diagnostic and therapeutic approaches.

Extracellular Vesicles in Metabolic Disorders

The involvement of extracellular vesicles (EVs) in metabolic disorders has been increasingly recognized, particularly in the context of their roles in modulating immune responses and influencing disease progression. A study highlighted how microbiota-reprogrammed phosphatidylcholine can inactivate cytotoxic CD8 T cells through UFMylation via exosomal SerpinB9 in multiple myeloma, indicating a complex interplay between gut microbiota, metabolism, and immune regulation (ref: Yan doi.org/10.1038/s41467-025-57966-5/). This suggests that targeting the microbiome and its metabolites could offer new therapeutic strategies for metabolic diseases. Additionally, menstrual fluid-derived small extracellular vesicles (MF-sEVs) have been investigated for their potential role in endometriosis pathogenesis, revealing that specific protein signatures in these vesicles may serve as biomarkers for this debilitating condition (ref: Gurung doi.org/10.1002/jev2.70048/). The modular approach for surface modification of sEVs using chimeric adaptor proteins also presents a promising avenue for enhancing the therapeutic efficacy of EVs in metabolic disorders (ref: Jang doi.org/10.1021/acsnano.4c15441/). These findings collectively emphasize the multifaceted roles of EVs in metabolic regulation and disease, highlighting their potential as both biomarkers and therapeutic targets.

Extracellular Vesicles in Regenerative Medicine

Extracellular vesicles (EVs) are increasingly recognized for their potential in regenerative medicine, particularly in tissue repair and regeneration. One innovative approach involves the use of bio-adhesive hybrid hydrogels conjugated with human induced pluripotent stem cell (hiPSC)-derived myofibers and their derived EVs, which demonstrated a combinational regenerative inductive effect for volumetric muscle regeneration (ref: Kim doi.org/10.1016/j.bioactmat.2024.09.013/). This study underscores the therapeutic potential of EVs in enhancing tissue regeneration and functional recovery. Moreover, a novel strategy employing a combined "eat me/don't eat me" approach using exosomes for acute liver injury treatment has been developed, leveraging the Wnt2 signaling pathway to promote hepatocyte proliferation post-injury (ref: Du doi.org/10.1016/j.xcrm.2025.102033/). This highlights the versatility of EVs in addressing complex regenerative challenges. Additionally, engineered EVs from LncEEF1G-overexpressing mesenchymal stem cells were shown to promote fibrotic liver regeneration by upregulating hepatic growth factor release from hepatic stellate cells, further illustrating the potential of EVs in modulating liver repair processes (ref: Zhang doi.org/10.1038/s12276-025-01413-4/). These findings collectively emphasize the transformative role of EVs in regenerative medicine, paving the way for novel therapeutic applications.

Extracellular Vesicles in Infectious Diseases

Extracellular vesicles (EVs) are gaining recognition for their roles in infectious diseases, particularly in understanding pathogen interactions and host responses. A study utilizing a skin organoid-based infection platform identified a specific inhibitor for hand, foot, and mouth disease (HFMD), highlighting the potential of EVs in drug discovery and pathogen biology (ref: Li doi.org/10.1038/s41467-025-57610-2/). This approach underscores the utility of EVs in modeling infections and facilitating the development of targeted therapies. Additionally, research into the dynamics of unspliced HIV-1 RNA revealed that nuclear retention acts as a reversible post-transcriptional block in latency, with implications for therapeutic strategies aimed at viral reactivation (ref: Dorman doi.org/10.1038/s41467-025-57290-y/). The enhanced packaging of U6 small nuclear RNA into EVs during HIV infection further illustrates the complex interplay between EVs and viral pathogenesis (ref: Huang doi.org/10.1126/sciadv.adq6557/). These findings collectively highlight the multifaceted roles of EVs in infectious diseases, offering insights into both pathogen biology and potential therapeutic interventions.

Extracellular Vesicles in Biomarker Discovery

Extracellular vesicles (EVs) are emerging as valuable tools in biomarker discovery, particularly in the context of cancer and other diseases. A notable study demonstrated the potential of fecal extracellular vesicle microRNA signatures (FEVOR) as non-invasive biomarkers for colorectal cancer (CRC), utilizing machine learning to enhance detection accuracy (ref: Zhang doi.org/10.1021/acsnano.4c16698/). This innovative approach underscores the promise of EVs in early cancer detection and personalized medicine. Furthermore, the analysis of lipid content in EV preparations has been highlighted as crucial for understanding their biological roles and potential as biomarkers (ref: Skotland doi.org/10.1002/jev2.70049/). The integration of advanced analytical techniques, such as mass spectrometry, allows for comprehensive profiling of EV lipidomes, which can provide insights into disease states and therapeutic responses. These findings collectively emphasize the transformative potential of EVs in biomarker discovery, paving the way for novel diagnostic and therapeutic strategies.

Extracellular Vesicles in Gene Therapy

Extracellular vesicles (EVs) are increasingly recognized for their potential in gene therapy, particularly in facilitating the delivery of therapeutic nucleic acids. A study comparing the horizontal gene transfer potential of EVs and viral-like particles revealed that both play significant roles in marine habitats, suggesting that EVs could be harnessed for gene delivery applications (ref: Biller doi.org/10.1038/s41467-025-57276-w/). This highlights the versatility of EVs as vehicles for genetic material transfer, which could be leveraged in therapeutic contexts. Additionally, advancements in nanoscopic profiling of small EVs via high-speed atomic force microscopy (HS-AFM) have provided new insights into their structural characteristics and functional roles (ref: Sandira doi.org/10.1002/jev2.70050/). This methodological innovation enhances our understanding of EV biology and their potential applications in gene therapy. Furthermore, the identification of podoplanin-positive cell-derived EVs contributing to cardiac amyloidosis post-myocardial infarction illustrates the multifaceted roles of EVs in both disease processes and potential therapeutic interventions (ref: Cimini doi.org/10.1016/j.celrep.2025.115408/). These findings collectively underscore the transformative potential of EVs in gene therapy and regenerative medicine.

Key Highlights

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