ArticleFluids and barriers of the CNS2021
Investigating receptor-mediated antibody transcytosis using blood-brain barrier organoid arrays.
Article in Fluids and barriers of the CNS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Vascularized Brain Organoids: Advances in Engineering Human Neurovascular Models.International journal of stem cells · 2026Review
- Blood‒brain barrier permeability assessment: from biomimetic models to multimodal imaging.Journal of Zhejiang University. Science. B · 2026Review
- Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- HumanBioactive materials · 2026Article
- Translational applicability of human blood-brain barrier spheroid models for the development of brain-penetrant therapeutic antibodies.Fluids and barriers of the CNS · 2026Article
- Improved targeted delivery of antisense oligonucleotide with an antibody mask.Nucleic acids research · 2025Article
- ApoE4 disrupts intracellular trafficking and iron homeostasis in a reproducible iPSC-based model of human brain endothelial cells.Stem cell reports · 2025Article
- Crossing Barriers: Advancements in Macromolecular Therapeutics for Neurodegenerative Diseases and Strategies to Overcome the Blood-Brain Barrier.ACS pharmacology & translational science · 2025Review
- Crossing the Blood-Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies.Pharmaceutics · 2025Review
- Advanced tissue technologies of blood-brain barrier organoids as high throughput toxicity readouts in drug development.Heliyon · 2025Article
- Harnessing Organoid Platforms for Nanoparticle Drug Development.Drug design, development and therapy · 2025Review
- Advances in Hydrogels of Drug Delivery Systems for the Local Treatment of Brain Tumors.Gels (Basel, Switzerland) · 2024Review
- Blood-Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The Progress in Molecular Transport and Therapeutic Development in Human Blood-Brain Barrier Models in Neurological Disorders.Cellular and molecular neurobiology · 2024Review
- Breaking the barrier: Nanoparticle-enhanced radiotherapy as the new vanguard in brain tumor treatment.Frontiers in pharmacology · 2024Review
- Exploring adjunctive therapies for cerebral malaria.Frontiers in cellular and infection microbiology · 2024Review
- Nanoparticle-Based Drug Delivery Systems Enhance Treatment of Cognitive Defects.International journal of nanomedicine · 2024Review
- Microfluidic models of the neurovascular unit: a translational view.Fluids and barriers of the CNS · 2023Review
- Receptor-Targeted Carbon Nanodot Delivery through Polymer Caging and Click Chemistry-Supported LRP1 Ligand Attachment.Polymers · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe pathways that control protein transport across the blood-brain barrier (BBB) remain poorly characterized. Despite great advances in recapitulating the human BBB in vitro, current models are not suitable for systematic analysis of the molecular mechanisms of antibody transport. The gaps in our mechanistic understanding of antibody transcytosis hinder new therapeutic delivery strategy development.
methodsWe applied a novel bioengineering approach to generate human BBB organoids by the self-assembly of astrocytes, pericytes and brain endothelial cells with unprecedented throughput and reproducibility using micro patterned hydrogels. We designed a semi-automated and scalable imaging assay to measure receptor-mediated transcytosis of antibodies. Finally, we developed a workflow to use CRISPR/Cas9 gene editing in BBB organoid arrays to knock out regulators of endocytosis specifically in brain endothelial cells in order to dissect the molecular mechanisms of receptor-mediated transcytosis.
resultsBBB organoid arrays allowed the simultaneous growth of more than 3000 homogenous organoids per individual experiment in a highly reproducible manner. BBB organoid arrays showed low permeability to macromolecules and prevented transport of human non-targeting antibodies. In contrast, a monovalent antibody targeting the human transferrin receptor underwent dose- and time-dependent transcytosis in organoids. Using CRISPR/Cas9 gene editing in BBB organoid arrays, we showed that clathrin, but not caveolin, is required for transferrin receptor-dependent transcytosis.
conclusionsHuman BBB organoid arrays are a robust high-throughput platform that can be used to discover new mechanisms of receptor-mediated antibody transcytosis. The implementation of this platform during early stages of drug discovery can accelerate the development of new brain delivery technologies.
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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.