ArticleStem cell research & therapy2022
Bone marrow mesenchymal stromal cells in a 3D system produce higher concentration of extracellular vesicles (EVs) with increased complexity and enhanced neuronal growth properties.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in Ocular Surface Disorders.Translational vision science & technology · 2026Pooled it
- Additive Manufacturing for Extracellular Vesicle Therapeutics: Engineering Strategies for Production, Isolation, and Delivery.Advanced healthcare materials · 2026Review
- A Hydrodynamic Bioreactor for High-Yield Production of Extracellular Vesicles from Stem Cell Spheroids with Defined Cargo Profiling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Corneal Nerve Regeneration via MSC-Derived EVs: Tissue Source and Culture Dimensionality Dictate miRNA Cargo and Therapeutic Efficacy.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Exosomes in corneal diseases: advances in diagnosis and therapy.Frontiers in cell and developmental biology · 2026Review
- Mesenchymal stem cell-derived extracellular vesicles for dry eye disease: principles, progress, and challenges.Extracellular vesicles and circulating nucleic acids · 2026Review
- Aging and Corneal Nerve Health: Mechanisms of Degeneration and Emerging Therapies for the Cornea.Cells · 2025Review
- Extracellular vesicles derived from different brain tissue cells: A potential therapeutic measure for hypoxic-ischemic brain injury in immature brains.Histology and histopathology · 2025Review
- Mesenchymal stem cell-derived apoptotic vesicles: emerging cell-free strategy for periodontitis treatment.Journal of nanobiotechnology · 2025Review
- Recent Insights into Organoid-Derived Extracellular Vesicles and Their Biomedical Applications.Journal of personalized medicine · 2025Review
- Review
- Extracellular Vesicle Secretion from 3D Culture of Human Adipose-Derived Mesenchymal Stem Cells in Scalable Bioreactors.Bioengineering (Basel, Switzerland) · 2025Article
- Review
- Continuous collection of human mesenchymal-stromal-cell-derived extracellular vesicles from a stirred tank reactor operated under xenogeneic-free conditions for therapeutic applications.Stem cell research & therapy · 2025Article
- Effects of Hydrogels on Mesenchymal Stem/Stromal Cells Paracrine Activity and Extracellular Vesicles Production.Journal of extracellular vesicles · 2025Review
- Advancements in extracellular vesicles biomanufacturing: a comprehensive overview of large-scale production and clinical research.Frontiers in bioengineering and biotechnology · 2025Review
- Scalability of spheroid-derived small extracellular vesicles production in stirred systems.Frontiers in bioengineering and biotechnology · 2025Article
- Boosting the Therapeutic Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells via Advanced Preconditioning for Neurodegenerative Disorders.Stem cells international · 2025Review
- Tailored Extracellular Vesicles from Dental Stem Cells: Advances in Specific Modifications for Enhanced Therapeutic Applications.International journal of nanomedicine · 2025Review
- High-yield BMSC-derived exosomes by the 3D culture system to enhance the skin wound repair.Regenerative biomaterials · 2025Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeExtracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) have been demonstrated to possess great potential in preclinical models. An efficient biomanufacturing platform is necessary for scale up production for clinical therapeutic applications. The aim of this study is to investigate the potential differences in neuro-regenerative properties of MSC-derived EVs generated in 2D versus 3D culture systems.
methodHuman bone marrow MSCs (BM-MSCs) were cultured in 2D monolayer and 3D bioreactor systems. EVs were isolated using ultracentrifugation followed by size and concentration measurements utilizing dynamic light scattering (NanoSight) and by fluorescence staining (ExoView). Mouse trigeminal ganglia (TG) neurons were isolated from BALB/c mice and cultured in the presence or absence of EVs derived from 2D or 3D culture systems. Neuronal growth and morphology were monitored over 5 days followed by immunostaining for β3 tubulin. Confocal images were analyzed by Neurolucida software to obtain the density and length of the neurites.
resultsThe NanoSight tracking analysis revealed a remarkable increase (24-fold change) in the concentration of EVs obtained from the 3D versus 2D culture condition. ExoView analysis showed a significantly higher concentration of CD63, CD81, and CD9 markers in the EVs derived from 3D versus 2D conditions. Furthermore, a notable shift toward a more heterogeneous phenotype was observed in the 3D-derived EVs compared to those from 2D culture systems. EVs derived from both culture conditions remarkably induced neurite growth and elongation after 5 days in culture compared to untreated control. Neurolucida analysis of the immunostaining images (β3 tubulin) showed a significant increase in neurite length in TG neurons treated with 3D- versus 2D-derived EVs (3301.5 μm vs. 1860.5 μm, P < 0.05). Finally, Sholl analysis demonstrated a significant increase in complexity of the neuronal growth in neurons treated with 3D- versus 2D-derived EVs (P < 0.05).
conclusionThis study highlights considerable differences in EVs obtained from different culture microenvironments, which could have implications for their therapeutic effects and potency. The 3D culture system seems to provide a preferred environment that modulates the paracrine function of the cells and the release of a higher number of EVs with enhanced biophysical properties and functions in the context of neurite elongation and growth.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.