extracellular vesicle

Overview

Extracellular vesicles (EVs) are membrane-enclosed particles released by cells into the extracellular space. They include subtypes such as exosomes and microvesicles, and they function as carriers of proteins, lipids, Metabolites, and nucleic acids between cells. In biomedical research, EVs are widely studied as mediators of intercellular communication, immune regulation, tissue remodeling, and organ crosstalk. Because they circulate in body fluids and reflect the state of their cells of origin, they are also of interest as minimally invasive biomarkers.

Recent work has expanded EV research into both mechanistic biology and translational technology. EVs have been investigated as natural delivery vehicles for curcumin, cannabidiol, siRNA, miRNA inhibitors, and proteins such as hypoxia-inducible factor-1α, as well as engineered platforms for cancer immunotherapy, fibrosis, asthma, stroke, neurodegeneration, and regenerative medicine. Their biological roles are closely linked to pathways involving PI3K/AKT, PTEN, mTOR, NLRP3 inflammasome signaling, ferroptosis, macrophage polarization, and dendritic cell modulation, making EVs a central technology in cell-free therapy and liquid biopsy development.

Focus of Latest Publications

Recent publications have established extracellular vesicles derived from mesenchymal stem cells and other cellular sources as multifunctional therapeutic platforms for diverse regenerative medicine applications. Bone marrow mesenchymal stem cell-derived EVs have demonstrated efficacy in spinal cord injury, with PRP-primed formulations inhibiting neuronal apoptosis and autophagy while promoting nerve regeneration through the miR-29a-3p/PTEN/PI3K/Akt/mTOR signaling axis. Similarly, human umbilical cord mesenchymal stem cell-derived exosomes have shown promise in alleviating neuropathic pain by modulating microglial and macrophage polarization and downregulating the NLRP3 inflammasome, with evidence suggesting miR-223-3p-dependent mechanisms of neuroprotection.

Adipose-derived stem cell-derived EVs demonstrate significant translational potential for cutaneous wound regeneration when produced in mechanically tunable hybrid hydrogels that enable modified molecular cargo composition and sustained release kinetics. Periodontal applications include exosomes from periodontal ligament stem cells loaded onto piezoelectric fibrous membranes, which synergistically enhance both angiogenesis and osteogenesis for vascularized bone regeneration. These regenerative applications highlight a broader pattern wherein EV molecular composition—including enrichment in regenerative-associated protein signatures and specific miRNA cargo—directly correlates with enhanced tissue-specific repair outcomes compared to conventionally cultured preparations.

Circulating EVs have emerged as non-invasive biomarkers reflecting pathophysiological changes across multiple disease states. In cirrhosis, circulating EVs mirror disease severity and thrombo-inflammatory, endothelial, and tissue-remodeling changes. Metabolic dysfunction-associated steatohepatitis demonstrates disease-specific EV protein signatures (including SLC27A5, HP, and CXCL7) detectable in patient serum and recapitulated in primary hepatocyte and organoid models, with machine learning approaches achieving diagnostic accuracy exceeding 0.97. Additionally, serum EV glycosylation patterns and proteomic signatures show diagnostic utility for gastric cancer peritoneal metastasis and Parkinson's disease when analyzed via electrochemiluminescence sensing and surface-enhanced Raman spectroscopy coupled with machine learning classification.

Engineering strategies have expanded EV therapeutic potential through biomaterial integration and molecular modification. Photocurable hydrogel platforms enable tunable control of EV secretion, cargo composition, and release kinetics from source cells while simultaneously serving as delivery scaffolds. CRISPR-based metabolic engineering combined with EVs delivering miRNAs and metabolic modulators synergistically promotes cardiac maturation in induced pluripotent stem cell-derived cardiomyocytes by enhancing mitochondrial biogenesis and oxidative phosphorylation capacity. Plant-derived extracellular vesicles from Ligusticum sinense function as dual-action nanoplatforms combining intrinsic phytochemical-mediated metabolic reprogramming with blood-brain barrier penetration, demonstrating superior efficacy in ischemic stroke repair when loaded with additional neuroprotectant agents.

Immunotherapeutic applications have positioned EV-based platforms as alternatives to whole-cell therapies. dendritic cell-derived EVs serve as nanoparticle platforms for cancer immunotherapy by transferring immunogenic molecules and processed antigens to T lymphocytes through paracrine mechanisms, with engineered variants showing enhanced immunotherapeutic potential. Clinical translation is advancing as demonstrated by expanded access safety data in COVID-19 respiratory failure, where bone marrow mesenchymal stem cell-derived EV secretome achieved favorable safety profiles with meaningful improvements in ventilation-free days and hospital discharge timelines.

Key Publications

• NEWJul Tunable bio-inspired hybrid hydrogels reprogram stem cell-derived extracellular vesicles for superior wound regeneration. (Biomaterials science, 2026, PMID 42383565): "Clinical translation of adipose-derived stem cell (ADSC)-derived extracellular vesicles (EVs) for cutaneous regeneration is challenged by variable secretion levels, heterogeneous molecular cargo, and inconsistent therapeutic potency."
• NEWJun Extracellular Vesicles From Young Brain-Mediated Delivery of PRDX3 Ameliorates Alveolar Bone Loss in Periodontitis. (Journal of clinical periodontology, 2026, PMID 42375016): "To elucidate the influence and mechanism of extracellular vesicles (EVs) derived from brain tissue with ageing regulating alveolar bone resorption in periodontitis."
• Jul Extracellular Vesicles Reflect Thrombo-Inflammatory, Endothelial and Tissue-Remodelling Changes in Cirrhosis. (Liver international : official journal of the International Association for the Study of the Liver, 2026, PMID 42249626): "Circulating extracellular vesicles (EVs) have emerged as potential biomarkers reflecting these pathophysiological processes."
• Jun Profiling of extracellular vesicles from primary hepatocytes, organoids, and mash patients identifies cell injury-specific signatures. (Scientific reports, 2026, PMID 42236744): "This study identifies biologically relevant extracellular vesicle (EV) protein signatures associated with MASH using patient serum, primary human hepatocytes (PHH), and human liver organoids (HLO)."
• May Platelet-rich plasma-primed bone marrow mesenchymal stem cell-derived exosomes inhibit neuronal apoptosis and autophagy, and promote nerve regeneration via the miR-29a-3p/PTEN/PI3K/Akt/mTOR axis after spinal cord injury. (Journal of molecular histology, 2026, PMID 42165939): "Both platelet-rich plasma (PRP) and exosomes derived from bone marrow mesenchymal stem cells (BMSCs) exhibit therapeutic potential for spinal cord injury (SCI)."
• May Selective Recognition of Tumor-Derived EVs by EpCAM-Imprinted Polymers for Proteomic Biomarker Discovery. (Analytical chemistry, 2026, PMID 42117374): "EpCAM, a key biomarker for epithelial tumors, is overexpressed in multiple cancers and enriched on tumor-derived extracellular vesicles (EVs), positioning it as a promising liquid biopsy target."
• May Bone Marrow Mesenchymal Stem Cell Extracellular Vesicle Treatment of Respiratory Failure from COVID-19: Endpoint Analysis of Expanded Access Safety Trial. (Stem cell reviews and reports, 2026, PMID 42113080): "The safety of an extracellular vesicle (EV) enriched secretome from bone marrow mesenchymal stem cells (BM-MSCs) was evaluated in a multi-site, prospective, expanded access trial as potential treatment for respiratory failure due to COVID-19."
• Apr Application of dendritic cell extracellular vesicles as a valid nanoparticle platform for cancer therapies: a narrative review. (Stem cell research & therapy, 2026, PMID 42010708): "Extracellular vesicles (EVs) are nanosized particles and are used for cell-free approaches instead of direct whole cell-based administration."
• May Human Periodontal Ligament Cells Exosome-Loaded Biodegradable Piezoelectric Fibrous Membrane for Vascularized Periodontal Bone Regeneration. (ACS biomaterials science & engineering, 2026, PMID 42012481): "As a cell-free therapeutic approach, exosomes (Exos) derived from PDLSCs represent a promising and effective cell-free therapeutic strategy for inducing neo-bone growth."
• May Biological Optical Nanocavity-Coupled Electrochemiluminescence Sensor for the Detection of Extracellular Vesicle Glycosylation in Gastric Cancer Diagnosis. (ACS sensors, 2026, PMID 41988862): "Analyzing the relationship between membrane curvature and biomolecules of extracellular vesicles (EVs) is crucial for understanding their functions."