ArticleFluids and barriers of the CNS2020
Inhibition of transforming growth factor beta signaling pathway promotes differentiation of human induced pluripotent stem cell-derived brain microvascular endothelial-like cells.
Article in Fluids and barriers of the CNS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed.
- Nanoscopic analysis of tight junction organization in in vitro blood-brain barrier models.Fluids and barriers of the CNS · 2026Article
- Endothelial-to-Mesenchymal Transition in Health and Disease: Molecular Insights and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Role of transforming growth factorβ in neurovascular unit during cerebral small vessel disease.Fluids and barriers of the CNS · 2025Review
- TGFβ family signaling in human stem cell self-renewal and differentiation.Cell regeneration (London, England) · 2024Review
- Synergistic induction of blood-brain barrier properties.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway.Fluids and barriers of the CNS · 2024Article
- Cerebral microvascular density, blood-brain barrier permeability, and support for neuroinflammation indicate early aging in a Marfan syndrome mouse model.Frontiers in physiology · 2024Article
- Aβ42 treatment of the brain side reduced the level of flotillin from endothelial cells on the blood side via FGF-2 signaling in a blood-brain barrier model.Molecular brain · 2023Article
- Article
- Hypoxia-induced blood-brain barrier dysfunction is prevented by pericyte-conditioned media via attenuated actomyosin contractility and claudin-5 stabilization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Recent Neurotherapeutic Strategies to Promote Healthy Brain Aging: Are we there yet?Aging and disease · 2022Review
- Study of BBB Dysregulation in Neuropathogenicity Using Integrative Human Model of Blood-Brain Barrier.Frontiers in cellular neuroscience · 2022Review
- Next-generation in vitro blood-brain barrier models: benchmarking and improving model accuracy.Fluids and barriers of the CNS · 2021Article
- Multi-disciplinary Approach for Drug and Gene Delivery Systems to the Brain.AAPS PharmSciTech · 2021Review
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5 authors.
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Abstract
backgroundThe blood-brain barrier (BBB) plays an important role as a biological barrier by regulating molecular transport between circulating blood and the brain parenchyma. In drug development, the accurate evaluation of BBB permeability is essential to predict not only the efficacy but also the safety of drugs. Recently, brain microvascular endothelial-like cells derived from human induced pluripotent stem cells (iPSCs) have attracted much attention. However, the differentiation protocol has not been optimized, and the enhancement of iPSC-derived brain microvascular endothelial-like cells (iBMELCs) function is required to develop highly functional BBB models for pharmaceutical research. Thus, we attempted to improve the functions of differentiated iBMELCs and develop a versatile BBB model by modulating TGF-β signaling pathway without implementing complex techniques such as co-culture systems.
methodsiPSCs were differentiated into iBMELCs, and TGF-β inhibitor was used in the late stage of differentiation. To investigate the effect of TGF-β on freezing-thawing, iBMELCs were frozen for 60-90 min or 1 month. The barrier integrity of iBMELCs was evaluated by transendothelial electrical resistance (TEER) values and permeability of Lucifer yellow. Characterization of iBMELCs was conducted by RT-qPCR, immunofluorescence analysis, vascular tube formation assay, and acetylated LDL uptake assay. Functions of efflux transporters were defined by intracellular accumulation of the substrates.
resultsWhen we added a TGF-β inhibitor during iBMELCs differentiation, expression of the vascular endothelial cell marker was increased and blood vessel-like structure formation was enhanced. Furthermore, TEER values were remarkably increased in three iPSC lines. Additionally, it was revealed that TGF-β pathway inhibition suppressed the damage caused by the freezing-thawing of iBMELCs.
conclusionWe succeeded in significantly enhancing the function and endothelial characteristics of iBMELCs by adding a small molecular compound, a TGF-β inhibitor. Moreover, the iBMELCs could maintain high barrier function even after freezing-thawing. Taken together, these results suggest that TGF-β pathway inhibition may be useful for developing iPSC-derived in vitro BBB models for further pharmaceutical research.
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