Differentiation of brain microvascular endothelial cells from human iPS cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20736
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition
• Principal Investigator: YAMAGUCHI Tomoko 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 幹細胞制御プロジェクト, 研究員 (50580130)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: BBB / P-gp / iPS細胞

Outline of Final Research Achievements

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 character. Therefore, more mature iBMECs by optimizing the differentiation protocol is beneficial for establishing a more reliable in vitro BBB model for studying central nervous system drug transport. Inducible SOX18 expression in iBMECs gained mature BBB phenotypes, including high TEER values and upregulation of P-gp expression. In addition, physiological barrier function and P-gp expression in BMECs can be enhanced by the canonical Wnt signaling activator. Our results may be useful for promoting the development of drugs for central nervous system diseases using in vitro BBB model

Free Research Field

幹細胞学

Academic Significance and Societal Importance of the Research Achievements

本研究により、より生体に近い脳血管内皮細胞をiPS細胞から作成可能となれば、iPS細胞由来脳血管内皮細胞が中枢神経疾患治療薬の開発において有用なツールになることが期待される。