Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling

Abstract The integral selectivity characteristic of the blood brain barrier (BBB) limits therapeutic options for many neurologic diseases and disorders. Currently, very little is known about the mechanisms that govern the dynamic nature of the BBB. Recent reports have focused on the development and...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Goodwell Nzou, R. T. Wicks, E. E. Wicks, S. A. Seale, C. H. Sane, A. Chen, S. V. Murphy, J. D. Jackson, A. J. Atala
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d0f27afeb18f49458be4b285d482ac08
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d0f27afeb18f49458be4b285d482ac08
record_format	dspace
spelling	oai:doaj.org-article:d0f27afeb18f49458be4b285d482ac082021-12-02T12:32:22ZHuman Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling10.1038/s41598-018-25603-52045-2322https://doaj.org/article/d0f27afeb18f49458be4b285d482ac082018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25603-5https://doaj.org/toc/2045-2322Abstract The integral selectivity characteristic of the blood brain barrier (BBB) limits therapeutic options for many neurologic diseases and disorders. Currently, very little is known about the mechanisms that govern the dynamic nature of the BBB. Recent reports have focused on the development and application of human brain organoids developed from neuro-progenitor cells. While these models provide an excellent platform to study the effects of disease and genetic aberrances on brain development, they may not model the microvasculature and BBB of the adult human cortex. To date, most in vitro BBB models utilize endothelial cells, pericytes and astrocytes. We report a 3D spheroid model of the BBB comprising all major cell types, including neurons, microglia and oligodendrocytes, to recapitulate more closely normal human brain tissue. Spheroids show expression of tight junctions, adherens junctions, adherens junction-associated proteins and cell specific markers. Functional assessment using MPTP, MPP+ and mercury chloride indicate charge selectivity through the barrier. Junctional protein distribution was altered under hypoxic conditions. Our spheroid model may have potential applications in drug discovery, disease modeling, neurotoxicity and cytotoxicity testing.Goodwell NzouR. T. WicksE. E. WicksS. A. SealeC. H. SaneA. ChenS. V. MurphyJ. D. JacksonA. J. AtalaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Goodwell Nzou R. T. Wicks E. E. Wicks S. A. Seale C. H. Sane A. Chen S. V. Murphy J. D. Jackson A. J. Atala Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling
description	Abstract The integral selectivity characteristic of the blood brain barrier (BBB) limits therapeutic options for many neurologic diseases and disorders. Currently, very little is known about the mechanisms that govern the dynamic nature of the BBB. Recent reports have focused on the development and application of human brain organoids developed from neuro-progenitor cells. While these models provide an excellent platform to study the effects of disease and genetic aberrances on brain development, they may not model the microvasculature and BBB of the adult human cortex. To date, most in vitro BBB models utilize endothelial cells, pericytes and astrocytes. We report a 3D spheroid model of the BBB comprising all major cell types, including neurons, microglia and oligodendrocytes, to recapitulate more closely normal human brain tissue. Spheroids show expression of tight junctions, adherens junctions, adherens junction-associated proteins and cell specific markers. Functional assessment using MPTP, MPP+ and mercury chloride indicate charge selectivity through the barrier. Junctional protein distribution was altered under hypoxic conditions. Our spheroid model may have potential applications in drug discovery, disease modeling, neurotoxicity and cytotoxicity testing.
format	article
author	Goodwell Nzou R. T. Wicks E. E. Wicks S. A. Seale C. H. Sane A. Chen S. V. Murphy J. D. Jackson A. J. Atala
author_facet	Goodwell Nzou R. T. Wicks E. E. Wicks S. A. Seale C. H. Sane A. Chen S. V. Murphy J. D. Jackson A. J. Atala
author_sort	Goodwell Nzou
title	Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling
title_short	Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling
title_full	Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling
title_fullStr	Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling
title_full_unstemmed	Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling
title_sort	human cortex spheroid with a functional blood brain barrier for high-throughput neurotoxicity screening and disease modeling
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/d0f27afeb18f49458be4b285d482ac08
work_keys_str_mv	AT goodwellnzou humancortexspheroidwithafunctionalbloodbrainbarrierforhighthroughputneurotoxicityscreeninganddiseasemodeling AT rtwicks humancortexspheroidwithafunctionalbloodbrainbarrierforhighthroughputneurotoxicityscreeninganddiseasemodeling AT eewicks humancortexspheroidwithafunctionalbloodbrainbarrierforhighthroughputneurotoxicityscreeninganddiseasemodeling AT saseale humancortexspheroidwithafunctionalbloodbrainbarrierforhighthroughputneurotoxicityscreeninganddiseasemodeling AT chsane humancortexspheroidwithafunctionalbloodbrainbarrierforhighthroughputneurotoxicityscreeninganddiseasemodeling AT achen humancortexspheroidwithafunctionalbloodbrainbarrierforhighthroughputneurotoxicityscreeninganddiseasemodeling AT svmurphy humancortexspheroidwithafunctionalbloodbrainbarrierforhighthroughputneurotoxicityscreeninganddiseasemodeling AT jdjackson humancortexspheroidwithafunctionalbloodbrainbarrierforhighthroughputneurotoxicityscreeninganddiseasemodeling AT ajatala humancortexspheroidwithafunctionalbloodbrainbarrierforhighthroughputneurotoxicityscreeninganddiseasemodeling
_version_	1718394122945953792

Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling

Ejemplares similares