RETRACTED: In Vitro Modeling of Blood-Brain Barrier with Human iPSC-Derived Endothelial Cells, Pericytes, Neurons, and Astrocytes via Notch Signaling

Kohei Yamamizu, Mio Iwasaki, Hitomi Takakubo, Takumi Sakamoto, Takeshi Ikuno, Mami Miyoshi, Takayuki Kondo, Yoichi Nakao, Masato Nakagawa, Haruhisa Inoue, Jun K. Yamashita

研究成果: Article査読

36 被引用数 (Scopus)

抄録

The blood-brain barrier (BBB) is composed of four cell populations, brain endothelial cells (BECs), pericytes, neurons, and astrocytes. Its role is to precisely regulate the microenvironment of the brain through selective substance crossing. Here we generated an in vitro model of the BBB by differentiating human induced pluripotent stem cells (hiPSCs) into all four populations. When the four hiPSC-derived populations were co-cultured, endothelial cells (ECs) were endowed with features consistent with BECs, including a high expression of nutrient transporters (CAT3, MFSD2A) and efflux transporters (ABCA1, BCRP, PGP, MRP5), and strong barrier function based on tight junctions. Neuron-derived Dll1, which activates Notch signaling in ECs, was essential for the BEC specification. We performed in vitro BBB permeability tests and assessed ten clinical drugs by nanoLC-MS/MS, finding a good correlation with the BBB permeability reported in previous cases. This technology should be useful for research on human BBB physiology, pathology, and drug development.

本文言語English
ページ(範囲)634-647
ページ数14
ジャーナルStem Cell Reports
8
3
DOI
出版ステータスPublished - 2017 3 14

ASJC Scopus subject areas

  • 生化学
  • 遺伝学
  • 発生生物学
  • 細胞生物学

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