A Retinoic Acid-enhanced, Multicellular Human Blood-brain Barrier Model Derived from Stem Cell Sources

Overview

Journal Sci Rep

Specialty Science

Date 2014 Feb 25

PMID 24561821

Citations 253

Authors

Ethan S Lippmann

Abraham Al-Ahmad

Samira M Azarin

Sean P Palecek

Eric V Shusta

Affiliations

Soon will be listed here.

Abstract

Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm(2)). Overall, this scalable human BBB model may enable a wide range of neuroscience studies.

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