ArticleFluids and barriers of the CNS2018
Modeling and rescue of defective blood-brain barrier function of induced brain microvascular endothelial cells from childhood cerebral adrenoleukodystrophy patients.
Article in Fluids and barriers of the CNS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Accelerated reprogramming of hiPSCs into functional brain endothelial-like cells using multiplexed CRISPR activation.Scientific reports · 2026Article
- HumanBioactive materials · 2026Article
- An AAV-Based Therapy Approach for Neurological Phenotypes of X-Linked Adrenoleukodystrophy.International journal of molecular sciences · 2025Review
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Restoring brain barriers: an innovative approach for treating neurological disorders.Fluids and barriers of the CNS · 2025Review
- Review
- Optical coherence tomography angiography reveals abnormal retinal vascular density and perfusion in patients with X-linked adrenoleukodystrophy: a cross-sectional study.Orphanet journal of rare diseases · 2025Article
- Easily misdiagnosed X-linked adrenoleukodystrophy.Italian journal of pediatrics · 2024Article
- The Blood-Brain Barrier Is Unaffected in theInternational journal of molecular sciences · 2024Article
- A novel human iPSC model of COL4A1/A2 small vessel disease unveils a key pathogenic role of matrix metalloproteinases.Stem cell reports · 2023Article
- Human-Induced Pluripotent Stem Cell-Based Model of the Blood-Brain at 10 Years: A Retrospective on Past and Current Disease Models.Handbook of experimental pharmacology · 2023Review
- Induced pluripotent stem cell-derived cells model brain microvascular endothelial cell glucose metabolism.Fluids and barriers of the CNS · 2022Article
- AnFrontiers in molecular neuroscience · 2022Article
- In Vitro Models of the Human Blood-Brain Barrier Utilising Human Induced Pluripotent Stem Cells: Opportunities and Challenges.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Advanced Human BBB-on-a-Chip: A New Platform for Alzheimer's Disease Studies.Advanced healthcare materials · 2021Review
- Peroxisomal ABC Transporters: An Update.International journal of molecular sciences · 2021Review
- Evolution of adrenoleukodystrophy model systems.Journal of inherited metabolic disease · 2021Review
- Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Patient-derived iPSC modeling of rare neurodevelopmental disorders: Molecular pathophysiology and prospective therapies.Neuroscience and biobehavioral reviews · 2021Review
- Human Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells: Current Controversies.Frontiers in physiology · 2021Article
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6 authors.
Funding
Abstract
backgroundX-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene. 40% of X-ALD patients will convert to the deadly childhood cerebral form (ccALD) characterized by increased permeability of the brain endothelium that constitutes the blood-brain barrier (BBB). Mutation information and molecular markers investigated to date are not predictive of conversion. Prior reports have focused on toxic metabolic byproducts and reactive oxygen species as instigators of cerebral inflammation and subsequent immune cell invasion leading to BBB breakdown. This study focuses on the BBB itself and evaluates differences in brain endothelium integrity using cells from ccALD patients and wild-type (WT) controls.
methodsThe blood-brain barrier of ccALD patients and WT controls was modeled using directed differentiation of induced pluripotent stem cells (iPSCs) into induced brain microvascular endothelial cells (iBMECs). Immunocytochemistry and PCR confirmed characteristic expression of brain microvascular endothelial cell (BMEC) markers. Barrier properties of iBMECs were measured via trans-endothelial electrical resistance (TEER), sodium fluorescein permeability, and frayed junction analysis. Electron microscopy and RNA-seq were used to further characterize disease-specific differences. Oil-Red-O staining was used to quantify differences in lipid accumulation. To evaluate whether treatment with block copolymers of poly(ethylene oxide) and poly(propylene oxide) (PEO-PPO) could mitigate defective properties, ccALD-iBMECs were treated with PEO-PPO block copolymers and their barrier properties and lipid accumulation levels were quantified.
resultsiBMECs from patients with ccALD had significantly decreased TEER (2592 ± 110 Ω cm
conclusionsThe finding that BBB integrity is decreased in ccALD and can be rescued with block copolymers opens the door for the discovery of BBB-specific molecular markers that can indicate the onset of ccALD and has therapeutic implications for preventing the conversion to ccALD.
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