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

Extracellular Vesicles in Cancer Progression

Recent studies have highlighted the role of extracellular vesicles (EVs) in cancer progression, particularly in the context of specific cancers such as breast and prostate cancer. One study demonstrated that exosomes derived from fatty liver tissue in mice preferentially accumulate in mammary adipocytes, fostering a pro-tumor microenvironment that correlates with increased breast cancer risk in individuals with nonalcoholic fatty liver disease (ref: Li doi.org/10.1016/j.cmet.2025.08.012/). Another investigation utilized a chemical glycoproteomic approach to analyze the surface proteins of urinary EVs, revealing potential biomarkers for prostate cancer diagnosis and grading, despite the technical challenges posed by the heterogeneity of EVs (ref: Cai doi.org/10.1002/anie.202509399/). Furthermore, the development of TMTP1-modified small EVs for targeted CRISPR/Cas9 delivery in BRAF-mutant anaplastic thyroid cancer showcased a novel strategy to overcome drug resistance, significantly enhancing treatment efficacy in both in vitro and in vivo models (ref: Zhang doi.org/10.1002/jev2.70170/). These findings collectively underscore the multifaceted roles of EVs in cancer biology, from facilitating tumor microenvironments to serving as diagnostic tools and therapeutic delivery vehicles. In addition to these findings, the role of cancer cell-secreted miR-33a was explored, revealing its involvement in reducing stress granule formation in the stroma, thereby promoting tumorigenesis under nutrient-deprived conditions (ref: Hu doi.org/10.1002/jev2.70153/). This highlights the intricate interplay between cancer cells and their microenvironment, mediated through EVs. The studies collectively emphasize the potential of targeting EVs and their cargo as a therapeutic strategy in cancer treatment, while also pointing to the need for further research into the mechanisms governing EV biogenesis and function.

Extracellular Vesicles in Neurodegenerative Diseases

The exploration of extracellular vesicles (EVs) in neurodegenerative diseases has gained momentum, particularly in understanding their role in conditions like Alzheimer's disease and amyotrophic lateral sclerosis (ALS). One study focused on the delivery of small interfering RNAs (siRNAs) targeting TDP-43, a protein associated with ALS and frontotemporal lobar degeneration, demonstrating that in vivo self-assembled siRNAs could ameliorate neurological pathology, thus presenting a promising therapeutic avenue (ref: Wu doi.org/10.1093/brain/). Additionally, the investigation into hippocampal spreading depolarization as a driver of postictal symptoms in epilepsy revealed significant insights into the neurobiological mechanisms underlying these conditions, utilizing advanced imaging and recording techniques (ref: Mitlasóczki doi.org/10.1126/scitranslmed.adv3260/). Moreover, the development of hydrogel systems loaded with aminoethyl anisamide-modified exosomes for targeting activated hepatic stellate cells illustrates the innovative applications of EVs in regenerative medicine, particularly in mitigating hepatic fibrosis (ref: Sun doi.org/10.1021/acsnano.5c06003/). This approach not only enhances the therapeutic potential of EVs but also addresses challenges related to their rapid clearance in systemic circulation. The collective findings from these studies emphasize the critical role of EVs in both the pathogenesis and potential treatment of neurodegenerative diseases, highlighting their utility as biomarkers and therapeutic agents.

Extracellular Vesicles in Inflammation and Immune Response

Extracellular vesicles (EVs) have emerged as pivotal players in mediating inflammation and immune responses, particularly in conditions such as osteoarthritis (OA). A study investigating the role of fibroblast-like synoviocyte (FLS)-derived EVs revealed significant alterations in exosomal pathways within OA synovium, with proteomic profiling identifying distinct molecular signatures that reflect the pathophysiological status of inflammatory and senescent FLSs (ref: Liu doi.org/10.1002/jev2.70162/). This highlights the potential of targeting these EVs for therapeutic relief in OA, emphasizing the need for further exploration of their role in disease progression. In addition, a genome-wide CRISPR/Cas9 screening identified the COMMANDER recycling complex as a key player in EV uptake, providing insights into the molecular mechanisms regulating EV internalization by target cells (ref: Palma-Cobo doi.org/10.1002/jev2.70166/). This understanding is crucial for enhancing the therapeutic delivery of EVs in inflammatory diseases. The studies collectively underscore the importance of EVs in modulating immune responses and their potential as therapeutic targets in inflammatory conditions.

Extracellular Vesicles in Tissue Regeneration and Repair

The therapeutic potential of extracellular vesicles (EVs) in tissue regeneration and repair has garnered significant attention, particularly in the context of conditions like hepatic fibrosis and intervertebral disc degeneration (IVDD). One innovative approach involved the development of a hydrogel loaded with aminoethyl anisamide-modified exosomes, which demonstrated efficacy in attenuating hepatic fibrosis by targeting activated hepatic stellate cells (ref: Sun doi.org/10.1021/acsnano.5c06003/). This study highlights the challenges of rapid clearance of EVs in systemic administration and presents a novel delivery platform to enhance their therapeutic effects. Additionally, research on mesenchymal stem cell-derived EVs indicated their potential in ameliorating temporomandibular joint osteoarthritis by suppressing osteoclast activity through the let-7a-5p/Integrin β3 axis (ref: Yang doi.org/10.1021/acsnano.5c11211/). This underscores the multifaceted roles of EVs in modulating inflammatory microenvironments and promoting tissue repair. Furthermore, the use of bioactive silk fibroin hydrogels to harness BMSCs-EVs for modulating macrophage polarization in IVDD illustrates the versatility of EV applications in regenerative medicine (ref: Liu doi.org/10.1002/jev2.70159/). Collectively, these findings emphasize the promise of EVs as therapeutic agents in tissue regeneration, warranting further investigation into their mechanisms of action and potential clinical applications.

Isolation and Characterization of Extracellular Vesicles

The isolation and characterization of extracellular vesicles (EVs) are critical for understanding their biological functions and therapeutic applications. A comparative assessment of various whole organ tissue processing methods for EV isolation highlighted the complexities involved in obtaining high-quality EVs from intact organs (ref: Hussain doi.org/10.1002/jev2.70127/). This study emphasizes the need for standardized protocols to enhance the reproducibility and reliability of EV research, particularly in translational applications. Moreover, the establishment of bona fide reference markers for genuine plant extracellular vesicles (PEVs) has paved the way for standardization in the field, providing comprehensive proteomic data from apoplastic washing fluid-EVs of reference plant species (ref: Rodríguez de Lope doi.org/10.1002/jev2.70147/). This foundational work is essential for advancing the understanding of PEVs and their roles in plant biology. The integration of these findings underscores the importance of rigorous characterization methods in EV research, which is crucial for unlocking their full potential in both therapeutic and research contexts.

Extracellular Vesicles in Metabolic Disorders

The role of extracellular vesicles (EVs) in metabolic disorders has been increasingly recognized, particularly in understanding their implications in conditions such as obesity and diabetes. One study identified gangliosides as key modulators of EV biogenesis, influencing the secretion of EVs and their cargo, which may play a role in cellular communication and metabolic regulation (ref: Monyror doi.org/10.1126/sciadv.ady5212/). This finding highlights the intricate relationship between EVs and metabolic pathways, suggesting that alterations in EV composition could impact metabolic health. Additionally, the exploration of EVs in the context of postictal symptoms in epilepsy revealed insights into the neurobiological mechanisms underlying these conditions, further emphasizing the interconnectedness of metabolic and neurological processes (ref: Mitlasóczki doi.org/10.1126/scitranslmed.adv3260/). The studies collectively underscore the potential of targeting EVs as a therapeutic strategy in metabolic disorders, while also pointing to the need for further research into their roles in disease pathogenesis and progression.

Extracellular Vesicles in Cardiovascular Diseases

Extracellular vesicles (EVs) have emerged as significant contributors to the understanding of cardiovascular diseases, particularly in the context of atherosclerosis and cancer. An integrated single-cell atlas of human atherosclerotic plaques revealed the complex immune mechanisms and structural cell transformations driving plaque progression, highlighting the potential of EVs as biomarkers for disease monitoring (ref: Traeuble doi.org/10.1038/s41467-025-63202-x/). This comprehensive analysis underscores the importance of EVs in elucidating the pathophysiology of cardiovascular diseases and their potential as therapeutic targets. Moreover, the modulation of the PPARγ pathway to enhance NECTIN4 expression in bladder cancer demonstrates the intersection of cancer biology and cardiovascular health, as NECTIN4 has emerged as a therapeutic target in urothelial carcinoma (ref: Chang doi.org/10.1038/s41467-025-62710-0/). This highlights the multifaceted roles of EVs in both cancer and cardiovascular contexts, suggesting that therapeutic strategies targeting EVs could have broad implications across various disease states.

Innovative Applications of Extracellular Vesicles

Innovative applications of extracellular vesicles (EVs) are being explored across various fields, particularly in therapeutic delivery and regenerative medicine. A genome-wide CRISPR/Cas9 screening identified the COMMANDER recycling complex as a key player in EV uptake, providing insights into the molecular mechanisms that regulate EV internalization by target cells (ref: Palma-Cobo doi.org/10.1002/jev2.70166/). This understanding is crucial for enhancing the efficacy of EV-based therapies, as it allows for the optimization of delivery systems to improve therapeutic outcomes. Additionally, the development of hydrogel systems loaded with aminoethyl anisamide-modified exosomes for targeting activated hepatic stellate cells illustrates the innovative use of EVs in addressing complex medical conditions such as hepatic fibrosis (ref: Sun doi.org/10.1021/acsnano.5c06003/). These advancements highlight the versatility of EVs as therapeutic agents, paving the way for their application in various clinical settings. The collective findings from these studies emphasize the potential of EVs to revolutionize therapeutic strategies, warranting further exploration into their mechanisms of action and clinical applications.

Key Highlights

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