ArticleJournal of nanobiotechnology2025
Engineered MSC-EVs loaded with BDNF-enhancing neuropeptides via a non-disruptive method enhance post-stroke neuroregeneration via intranasal delivery.
Article in Journal of nanobiotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Growth factor applications and clinical translation: advances and challenges.Annals of medicine · 2026Review
- Review
- Elucidating the multitarget neuroprotective mechanisms of protocatechuic acid in neurological disorders (Review).Molecular medicine reports · 2026Review
- Development of a rapid and simple Xeno Nucleic Acid (XNA) sensor-based microRNA detection platform for Parkinson's disease diagnostics.Journal of nanobiotechnology · 2026Article
- Advancing MSC-EV Therapies: Harnessing Preconditioning and Mito-EVs to Tackle Neuroinflammation and Neurodegeneration.Pharmaceutics · 2026Review
- Review
- Research progress of blood-brain barrier penetrating and brain diseases therapy by natural biopolymer - based nanomedicine delivery systems.Materials today. Bio · 2026Review
- Engineering integrin αvβ8-targeted extracellular vesicles to deliver BDNF mRNA for motor recovery in spinal cord injury.Journal of nanobiotechnology · 2026Article
- Delivery of TCM Monomers Using Blood Cell Membrane Coated Biomimetic Nanoparticles to Target CVD.International journal of nanomedicine · 2026Review
- Extracellular vesicles for Alzheimer's disease therapy: mechanisms, engineering strategies, and clinical translation.Extracellular vesicles and circulating nucleic acids · 2026Review
- Engineered mesenchymal stem cell-derived extracellular vesicles as programmable biomaterial platforms for liver fibrosis: design principles, manufacturing and clinical translation.Frontiers in bioengineering and biotechnology · 2026Review
- Current State of the Neurotrophin-Based Pharmaceutics in the Treatment of Neurodegenerative Diseases and Neuroinflammation.Medical sciences (Basel, Switzerland) · 2025Review
- Atosiban-conjugated 3WJ-pRNA nanoparticles delivering GAS1-enhanced extracellular vesicles: targeting the decidua to combat recurrent miscarriage.Journal of nanobiotechnology · 2025Article
- Neuropeptide TIP39 as a pluripotent brain molecule and its potential functions in postpartum depression.Frontiers in endocrinology · 2025Review
- Global research hotspots and trends in microglia in ischemic stroke.Frontiers in immunology · 2025Article
- Exosomal lncRNA MIAT enriched in M2 macrophages contributes to electroacupuncture-driven peripheral nerve regeneration through targeting MiR-130a-3p/KLF7.Frontiers in neurologyArticle
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show potential as neuroregenerative therapies. Incorporating bioactive compounds such as neuropeptides that enhance brain-derived neurotrophic factor (BDNF) expression may amplify their therapeutic potential. We developed a clinical-scale method for loading neuropeptides into MSC-EVs, while preserving their structural integrity and therapeutic functionality. Through scalable 3D bioprocessing, we produced high-purity MSC-EVs and evaluated loading methods for encapsulating neuropeptides and full-length BDNF. EVs were characterized using electron microscopy, nanoparticle tracking analysis, and 3D STORM microscopy. The cellular uptake, distribution, and biological effects of neuropeptide-loaded MSC-EVs were tested in vitro and in vivo. Passive incubation was the optimal loading method for maintaining EV integrity while achieving effective neuropeptide encapsulation. Active loading methods destabilized the EV membrane despite higher encapsulation efficiency. Neuropeptide-loaded MSC-EVs crossed the blood-brain barrier (BBB) and significantly enhanced BDNF expression, neurogenesis, and neuroprotection in vitro, ex vivo, and in vivo. Compared with HEK293-derived extracellular vesicles (HEK-EVs), MSC-EVs demonstrated superior regenerative effects. In a photothrombotic stroke model, intranasal administration of neuropeptide-loaded MSC-EVs reduced infarct size, improved neuronal survival, and activated neuroprotective pathways mediated by Cyclic AMP Response Element-Binding protein (CREB) phosphorylation. We established a clinically scalable approach for producing neuropeptide-loaded MSC-EVs with potential as next-generation, targeted neuroregenerative therapies for treating stroke and other neurological disorders. Importantly, the EVs used in this study were produced under clinically applicable conditions and characterized according to the Minimal Information for Studies of Extracellular Vesicles (MISEV) 2023 guidelines.
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