ArticleFluids and barriers of the CNS2023
The maturation of iPS cell-derived brain microvascular endothelial cells by inducible-SOX18 expression.
Article in Fluids and barriers of the CNS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- MFSD2A in health and disease: lysolipid transport, barrier physiology, and translational boundaries.Molecular biomedicine · 2026Review
- ETS-guided iPSC-endothelial models recapitulate malaria pathogenesis.EMBO molecular medicine · 2026Article
- Accelerated reprogramming of hiPSCs into functional brain endothelial-like cells using multiplexed CRISPR activation.Scientific reports · 2026Article
- Old World alphaviruses use distinct mechanisms to infect brain microvascular endothelial cells for neuroinvasion.Cell reports · 2025Article
- Review
- A genetically inducible endothelial niche enables vascularization of human kidney organoids with multilineage maturation and emergence of renin expressing cells.Kidney international · 2024Article
- Cellular heterogeneity and dynamics of the human uterus in healthy premenopausal women.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Generation and characterisation of scalable and stable human pluripotent stem cell-derived microvascular-like endothelial cells for cardiac applications.Angiogenesis · 2024Article
- Natural medicinal compounds target signal transduction pathways to overcome ABC drug efflux transporter-mediated multidrug resistance in cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- Genetically engineering endothelial niche in human kidney organoids enables multilineage maturation, vascularization and de novo cell types.bioRxiv : the preprint server for biology · 2023Article
- Genetic disorders and genetic manipulation at the blood-brain barriers.Fluids and barriers of the CNS · 2023Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBrain microvascular endothelial cells (BMECs) play a major role in the blood-brain barrier (BBB), and are critical for establishing an in vitro BBB model. Currently, iPSC-derived BMECs (iBMECs) have been used to construct in vitro BBB models with physiological barrier functions, such as high trans-endothelial electrical resistance (TEER) and expression of transporter proteins. However, the relatively low p-glycoprotein (P-gp) level and a decrease in the efflux ratio of its substrates in iBMECs suggest their immature nature. Therefore, more mature iBMECs by optimizing the differentiation induction protocol is beneficial for establishing a more reliable in vitro BBB model for studying central nervous system (CNS) drug transport.
methodsTo identify human brain endothelial cell fate-inducing factors, HUVEC was transfected with Zic3A-, Zic3B-, and Sox18-expressing lentivirus vector. Since SOX18 was found to induce BMEC properties, we used a Dox-inducible Tet-on system to express SOX18 during iBMEC differentiation and explored the impact of SOX18 expression on iBMEC maturation.
resultsSox18-mediated iBMECs achieved a higher TEER value than normal iBMECs (> 3000 Ω cm
conclusionsInducible SOX18 expression in iBMECs gained BBB phenotypes, including high TEER values and upregulation of tight junction-related genes, endothelial cell (EC) markers, BBB transporters, and higher cell viability after treatment with puromycin. Collectively, we provide a differentiation method for the maturation of human iPS cell-derived BMECs with SOX18 expression, describing its contribution to form an in vitro BBB model for CNS drug transport studies.
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