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US 2017/0362584 A1Published application
Human blood brain barrier model
AssigneeNational Research Council of Canada
InventorsMahmud Bani, Danica Stanimirovic, Maria Ribecco-Lutkiewicz
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Abstract
An in vitro population of human brain endothelial cells (hBECs) expressing claudin-5, occludin, ZO-1 and GLUT-1 and expressing one or more of FZD7, WNT7A, WNT7B, APCDD1, STRA6 and ZO-3 is provided. A blood brain barrier (BBB) comprising the hBECs and use of the BBB for analyzing permeability characteristics of a test agent are provided.
Claims29
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A method of generating human brain endothelial cells (hBECs), the method comprising:
- a. providing amniotic fluid (AF) cells;
- b. reprogramming the AF cells into induced pluripotent stem cells (iPSCs), thereby generating AF-iPSCs;
- c. differentiating the AF-iPSCs into hBECs, the hBECs expressing claudin-5, occludin, ZO-1 and GLUT-1 and expressing one or more of FZD7, WNT7A, WNT7B, APCDD1, STRA6 and ZO-3, and optionally expressing ABCG2, PGP and transferrin receptor;
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- d. expanding the hBECs.
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A blood brain barrier model comprising:
- a permeable support having a surface comprising extracellular matrix proteins;
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- a plurality of human brain endothelial cells (hBECs), the plurality of hBECs expressing claudin-5, occludin, ZO-1 and GLUT-1 and expressing one or more of FZD7, WNT7A, WNT7B, APCDD1, STRA6 and ZO-3, the hBECs being grown to confluence on the permeable support.
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Dependencies are inferred from the claim text.