ArticleJournal of advanced research2023
Advanced 3D dynamic culture system with transforming growth factor-β3 enhances production of potent extracellular vesicles with modified protein cargoes via upregulation of TGF-β signaling.
Article in Journal of advanced research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 29 citations in OpenAlex.
- From pathogenic to reparative: Context-Dependent function of extracellular vesicles in osteoarthritis.Bioactive materials · 2027Review
- Cisplatin-Resistant Lung Adenocarcinoma Cells Exhibit Increased Proangiogenic Capacity in a Microphysiological Model of Tumor Neovascularization.Cancer medicine · 2026Article
- Additive Manufacturing for Extracellular Vesicle Therapeutics: Engineering Strategies for Production, Isolation, and Delivery.Advanced healthcare materials · 2026Review
- Mechanochemically primed regenerative extracellular vesicles as a nanotherapeutic strategy for peripheral neuropathy.Journal of nanobiotechnology · 2026Article
- Kaempferol-modified mesenchymal stem cell extracellular vesicle-mimetics promote photoaging repair by suppressing ADAM10.Cell communication and signaling : CCS · 2026Article
- Engineering Mesenchymal Stem Cell Spheroids and Brain Organoids: Advanced 3D Culture Platforms for Neurodegenerative Disease Cell Therapy.Stem cell reviews and reports · 2026Review
- Priming strategies to enhance the therapeutic efficacy of mesenchymal stromal/stem cell-derived vesicles in regenerative medicine.Extracellular vesicles and circulating nucleic acids · 2026Review
- Decellularized extracellular matrix restores Fibronectin/Integrin β1 balance through extracellular vesicles to rejuvenate chondrocytes and alleviate osteoarthritis progression.Journal of orthopaedic translation · 2026Article
- Advances in enhanced mesenchymal stem cell technologies: innovations and therapeutic applications.Frontiers in cell and developmental biology · 2026Review
- Extracellular vesicles derived from salivary gland stem cells cultured on microwell scaffolds loaded with WNT3A promote the recovery of salivary gland function damaged by radiation via the YWHAZ-PI3K-AKT pathway.Bioactive materials · 2025Article
- Physicochemical Modulation Strategies for Mass Production of Extracellular Vesicle.Tissue engineering and regenerative medicine · 2025Review
- Therapeutic potential of NGF-enriched extracellular vesicles in modulating neuroinflammation and enhancing peripheral nerve remyelination.Acta neuropathologica communications · 2025Article
- CD9-enriched extracellular vesicles from chemically reprogrammed basal progenitors of salivary glands mitigate salivary gland fibrosis.Bioactive materials · 2025Article
- The proteomic landscape of extracellular vesicles derived from human intervertebral disc cells.JOR spine · 2024Article
- PKM2-Driven Lactate Overproduction Triggers Endothelial-To-Mesenchymal Transition in Ischemic Flap via Mediating TWIST1 Lactylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Extracellular derivatives for bone metabolism.Journal of advanced research · 2024Review
- Efficient Treatment of Psoriasis Using Conditioned Media from Mesenchymal Stem Cell Spheroids Cultured to Produce Transforming Growth Factor-International journal of stem cells · 2024Article
- Exosome-mediated renal protection: Halting the progression of fibrosis.Genes & diseases · 2024Review
- Exploring the potential of in vitro extracellular vesicle generation in reproductive biology.Journal of extracellular biology · 2024Review
- Therapeutics of the future: Navigating the pitfalls of extracellular vesicles research from an osteoarthritis perspective.Journal of extracellular vesicles · 2024Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMesenchymal stromal cells (MSCs) release extracellular vesicles (MSC-EVs) containing various cargoes. Although MSC-EVs show significant therapeutic effects, the low production of EVs in MSCs hinders MSC-EV-mediated therapeutic development.
objectivesHere, we developed an advanced three-dimensional (a3D) dynamic culture technique with exogenous transforming growth factor beta-3 (TGF-β3) treatment (T-a3D) to produce potent MSC-EVs.
methodsOur system enabled preparation of a highly concentrated EV-containing medium for efficient EV isolation and purification with higher yield and efficacy.
resultsMSC spheroids in T-a3D system (T-a3D spheroids) showed high expression of CD9 and TGF-β3, which was dependent on TGF-β signaling. Treatment with EVs produced under T-a3D conditions (T-a3D-EVs) led to significantly improved migration of dermal fibroblasts and wound closure in an excisional wound model. The relative total efficacy (relative yield of single-batch EVs (10-11-fold) × relative regeneration effect of EVs (2-3-fold)) of T-a3D-EVs was approximately up to 33-fold higher than that of 2D-EVs. Importantly the quantitative proteomic analyses of the T-a3D spheroids and T-a3D-EVs supported the improved EV production as well as the therapeutic potency of T-a3D-EVs.
conclusionTGF-β signalling differentially regulated by fluid shear stress produced in our system and exogenous TGF-β3 addition was confirmed to play an important role in the enhanced production of EVs with modified protein cargoes. We suggest that the T-a3D system leads to the efficient production of MSC-EVs with high potential in therapies and clinical development.
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Registered trials
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.