ArticleStem cell research & therapy2025
Biomanufacturing and lipidomics analysis of extracellular vesicles secreted by human blood vessel organoids in a vertical wheel bioreactor.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed.
- Injectable microsphere-based delivery strategies for stem cells and their derivatives in tissue regeneration.Bioactive materials · 2026Review
- Electrical Stimulation of Human Adipose Tissue-Derived Mesenchymal Stem Cells and Schwann Cells for Regulating Extracellular Vesicle Biogenesis and Inflammation.Bioengineering (Basel, Switzerland) · 2026Article
- Encapsulation and Controlled Release of Human Spinal Cord Organoid-Derived Extracellular Vesicles for Tissue Patterning in Viscoelastic Hyaluronic Acid Hydrogels.Advanced healthcare materials · 2026Article
- Bioprocess Design and Optimization of Extracellular Vesicles Derived from Mesenchymal Stromal Cells.ACS nano · 2026Article
- Machine learning for extracellular vesicles enables diagnostic and therapeutic nanobiotechnology.Journal of nanobiotechnology · 2026Review
- Organoids for disease modeling and treatment: state-of-the-art.Experimental hematology & oncology · 2026Review
- Mapping the Ischemic Continuum: Dynamic Multi-Omic Biomarker and AI for Personalized Stroke Care.International journal of molecular sciences · 2026Review
- Lipid metabolism and lipid signaling in extracellular vesicles ontogeny: from biogenesis to functional execution.Journal of nanobiotechnology · 2025Review
- Extracellular Vesicle Secretion from 3D Culture of Human Adipose-Derived Mesenchymal Stem Cells in Scalable Bioreactors.Bioengineering (Basel, Switzerland) · 2025Article
- Extracellular Vesicle Production from Human Blood Vessel Organoids in a Vertical Wheel Bioreactor.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Extracellular Vesicles as Emerging Therapeutic Strategies in Spinal Cord Injury: Ready to Go.Biomedicines · 2025Review
- Biomanufacturing and Curcumin-Loading of Human Choroid Plexus Organoid-Derived Extracellular Vesicles from a Vertical-Wheel Bioreactor to Alleviate Neuro-Inflammation.Biomedicines · 2025Article
- Engineering human bone marrow-derived mesenchymal stromal cell aggregates for enhanced extracellular vesicle secretion in a vertical-wheel bioreactor.Frontiers in bioengineering and biotechnology · 2025Article
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10 authors.
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Abstract
backgroundExtracellular vesicles (EVs) derived from human organoids are phospholipid bilayer-bound nanoparticles that carry therapeutic cargo. However, the low yield of EVs remains a critical bottleneck for clinical translation. Vertical-Wheel bioreactors (VWBRs), with unique design features, facilitate the scalable production of EVs secreted by human blood vessel organoids (BVOs) under controlled shear stress, using aggregate- and microcarrier-based culture systems.
methodsHuman induced pluripotent stem cell-derived BVOs cultured as aggregates or on Synthemax II microcarriers within VWBRs (40 and 80 rpm) were compared to static controls. The organoids were characterized by metabolite profiling, flow cytometry, and gene expression of EV biogenesis markers. EVs were characterized by nanoparticle tracking analysis, electron microscopy, and Western blotting. Lipidomics provided insights into EV lipid composition, while functional assays assessed the impact of EVs in a D-galactose-induced senescence model.
resultsVWBR cultures showed more aerobic metabolism and higher expression of EV biogenesis genes compared to the static control. EVs from different conditions were comparable in size, but the yields were significantly higher for microcarrier and dynamic cultures than static aggregates. Lipidomic profiling revealed minimal variation (< 0.36%) in total lipid content; however, distinct differences were identified in lipid chain lengths and saturation levels, affecting key pathways such as sphingolipid and neurotrophin signaling. Human BVO EVs demonstrated the abilities of reducing oxidative stress and increasing cell proliferation in vitro.
conclusionsHuman BVOs differentiated in VWBRs (in particular 40 rpm) produce 2-3 fold higher yield of EVs (per mL) than static control. The bio manufactured EVs from VWBRs have exosomal characteristics and therapeutic cargo, showing functional properties in in vitro assays. This innovative approach establishes VWBRs as a scalable platform for producing functional EVs with defined lipid profiles and therapeutic potential, paving the way for future in vivo studies.
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