An in vitro model for vitamin A transport across the human blood–brain barrier

Abstract

Vitamin A, supplied by the diet, is critical for brain health, but little is known about its delivery across the blood–brain barrier (BBB). Brain microvascular endothelial-like cells (BMECs) differentiated from human-derived induced pluripotent stem cells (iPSCs) form a tight barrier that recapitulates many of the properties of the human BBB. We paired iPSC-derived BMECs with recombinant vitamin A serum transport proteins, retinol-binding protein (RBP), and transthyretin (TTR), to create an in vitro model for the study of vitamin A (retinol) delivery across the human BBB. iPSC-derived BMECs display a strong barrier phenotype, express key vitamin A metabolism markers, and can be used for quantitative modeling of retinol accumulation and permeation. Manipulation of retinol, RBP, and TTR concentrations, and the use of mutant RBP and TTR, yielded novel insights into the patterns of retinol accumulation in, and permeation across, the BBB. The results described herein provide a platform for deeper exploration of the regulatory mechanisms of retinol trafficking to the human brain.