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Influence of basal media composition on barrier fidelity within human pluripotent stem cell‐derived blood‐brain barrier models

Title: Influence of basal media composition on barrier fidelity within human pluripotent stem cell‐derived blood‐brain barrier models
Authors: Neal, Emma H.; Katdare, Ketaki A.; Shi, Yajuan; Marinelli, Nicholas A.; Hagerla, Kameron A.; Lippmann, Ethan S.
Contributors: National Science Foundation; Chan Zuckerberg Initiative; BrightFocus Foundation; National Institutes of Health
Source: Journal of Neurochemistry ; volume 159, issue 6, page 980-991 ; ISSN 0022-3042 1471-4159
Publisher Information: Wiley
Publication Year: 2021
Collection: Wiley Online Library (Open Access Articles via Crossref)
Description: It is increasingly recognized that brain microvascular endothelial cells (BMECs), the principal component of the blood‐brain barrier (BBB), are highly sensitive to soluble cues from both the bloodstream and the brain. This concept extends in vitro, where the extracellular milieu can also influence BBB properties in cultured cells. However, the extent to which baseline culture conditions can affect BBB properties in vitro remains unclear, which has implications for model variability and reproducibility, as well as downstream assessments of molecular transport and disease phenotypes. Here, we explore this concept by examining BBB properties within human‐induced pluripotent stem cell (iPSC)‐derived BMEC‐like cells cultured under serum‐free conditions in DMEM/F12 and Neurobasal media, which have fully defined compositions. We demonstrate notable differences in both passive and active BBB properties as a function of basal media composition. Further, RNA sequencing and phosphoproteome analyses revealed alterations to various signaling pathways in response to basal media differences. Overall, our results demonstrate that baseline culture conditions can have a profound influence on the performance of in vitro BBB models, and these effects should be considered when designing experiments that utilize such models for basic research and preclinical assays. image
Document Type: article in journal/newspaper
Language: English
DOI: 10.1111/jnc.15532
Availability: https://doi.org/10.1111/jnc.15532; https://onlinelibrary.wiley.com/doi/pdf/10.1111/jnc.15532; https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jnc.15532; https://onlinelibrary.wiley.com/doi/am-pdf/10.1111/jnc.15532
Rights: http://onlinelibrary.wiley.com/termsAndConditions#am ; http://onlinelibrary.wiley.com/termsAndConditions#vor
Accession Number: edsbas.72EA5F8D
Database: BASE