ArticleCells2023
Free Bilirubin Induces Neuro-Inflammation in an Induced Pluripotent Stem Cell-Derived Cortical Organoid Model of Crigler-Najjar Syndrome.
Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Indirect bilirubin mitigates tubular vacuolization and injury in experimental contrast nephropathy.BMC nephrology · 2026Article
- Hyperbilirubinemia and phototherapy differentially alter hippocampal transcriptome in the preterm Gunn rat model.Pediatric research · 2026Article
- Brain Organoids: Emerging Platforms for Modern Neuroscience.Brain sciences · 2026Review
- Evidence for conserved expression of genes annotated as associated with brain-related biological processes in human podocytes and brain.BMC nephrology · 2026Article
- Polydopamine-mediated EGCG-modified polystyrene microspheres for the synergistic removal of inflammatory cytokines TNF-α and bilirubin in liver failure.Regenerative biomaterials · 2026Article
- Biomedical applications of organoids in genetic diseases.Medical review (2021) · 2025Review
- Genetically Modified Hepatocytes Targeting Bilirubin and Ammonia Metabolism for the Construction of Bioartificial Liver System.Biomaterials research · 2024Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bilirubin-induced neurological damage (BIND), which might progress to kernicterus, occurs as a consequence of defects in the bilirubin conjugation machinery, thus enabling albumin-unbound free bilirubin (BF) to cross the blood-brain barrier and accumulate within. A defect in the UGT1A1 enzyme-encoding gene, which is directly responsible for bilirubin conjugation, can cause Crigler-Najjar syndrome (CNS) and Gilbert's syndrome. We used human-induced pluripotent stem cell (hiPSC)-derived 3D brain organoids to model BIND in vitro and unveil the molecular basis of the detrimental effects of BF in the developing human brain. Healthy and patient-derived iPSCs were differentiated into day-20 brain organoids, and then stimulated with 200 nM BF. Analyses at 24 and 72 h post-treatment point to BF-induced neuro-inflammation in both cell lines. Transcriptome, associated KEGG, and Gene Ontology analyses unveiled the activation of distinct inflammatory pathways, such as cytokine-cytokine receptor interaction, MAPK signaling, and NFκB activation. Furthermore, the mRNA expression and secretome analysis confirmed an upregulation of pro-inflammatory cytokines such as IL-6 and IL-8 upon BF stimulation. This novel study has provided insights into how a human iPSC-derived 3D brain organoid model can serve as a prospective platform for studying the etiology of BIND kernicterus.
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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.