Human 3D In Vitro Models for Developmental Neurotoxicity

Smirnova, Lena; Hartung, Thomas

Human 3D In Vitro Models for Developmental Neurotoxicity

Files

There are no files associated with this item.

Date

2018

Authors

Smirnova, Lena

Hartung, Thomas

DOI (citable link)

10.1016/B978-0-12-809405-1.00014-6

Collections

Biologie

Publication type

Contribution to a collection

Publication status

Published

Published in

Handbook of Developmental Neurotoxicology / Slikker, William et al. (ed.). - Second edition. - London : Academic, 2018. - pp. 163-172. - ISBN 978-0-12-809405-1

Abstract

Developmental neurotoxicity (DNT) testing of industrial chemicals is an increasingly perceived societal need in light of strong increases in neurodevelopmental disorders including autism. The current testing approach for DNT in vivo does not satisfy these needs because despite enormous costs and animal use, there appears to be limited predictivity for its health effects in humans. The Center for Alternatives to Animal Testing (CAAT) in the United States and Europe along with its partners has steered a process of developing in vitro strategies for DNT, which is summarized here. This process has prioritized models, cellular key events, reference compounds, and others. This shaped a 3DNT approach, which aims to employ three-dimensional (3D) microphysiological models such as an induced pluripotent stem cells–derived mini-brain model from our laboratory. These complex models have to be complemented with, favorably 3D, models of homogenous cell models for pathway identification; an example of a 3D dopaminergic neurons (LUHMES) model is given. The human mini-brain model offers opportunities beyond studying developmental effects. It is also undergoing further amendments such as the addition of microglia and a blood–brain barrier. A major recent breakthrough showed that the model could be frozen for stockpiling and transport. This enables us to make the model readily available via commercial vendors. For this purpose, a Johns Hopkins spin-off biotech company, Organome LLC, was formed.

Subject (DDC)

570 Biosciences, Biology

Keywords

neurodevelopment; brain; cell culture; organoids; spheroids; microphysiological systems; mini-brain

Cite This

ISO 690

SMIRNOVA, Lena, Thomas HARTUNG, 2018. Human 3D In Vitro Models for Developmental Neurotoxicity. In: SLIKKER, William, ed. and others. Handbook of Developmental Neurotoxicology. Second edition. London:Academic, pp. 163-172. ISBN 978-0-12-809405-1. Available under: doi: 10.1016/B978-0-12-809405-1.00014-6

BibTex

@incollection{Smirnova2018Human-41991,
  year={2018},
  doi={10.1016/B978-0-12-809405-1.00014-6},
  title={Human 3D In Vitro Models for Developmental Neurotoxicity},
  edition={Second edition},
  isbn={978-0-12-809405-1},
  publisher={Academic},
  address={London},
  booktitle={Handbook of Developmental Neurotoxicology},
  pages={163--172},
  editor={Slikker, William},
  author={Smirnova, Lena and Hartung, Thomas}
}

RDF

<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/41991">
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/41991"/>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2018-04-10T08:44:17Z</dc:date>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:contributor>Hartung, Thomas</dc:contributor>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:creator>Hartung, Thomas</dc:creator>
    <dc:creator>Smirnova, Lena</dc:creator>
    <dc:language>eng</dc:language>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2018-04-10T08:44:17Z</dcterms:available>
    <dc:contributor>Smirnova, Lena</dc:contributor>
    <dcterms:issued>2018</dcterms:issued>
    <dcterms:abstract xml:lang="eng">Developmental neurotoxicity (DNT) testing of industrial chemicals is an increasingly perceived societal need in light of strong increases in neurodevelopmental disorders including autism. The current testing approach for DNT in vivo does not satisfy these needs because despite enormous costs and animal use, there appears to be limited predictivity for its health effects in humans. The Center for Alternatives to Animal Testing (CAAT) in the United States and Europe along with its partners has steered a process of developing in vitro strategies for DNT, which is summarized here. This process has prioritized models, cellular key events, reference compounds, and others. This shaped a 3DNT approach, which aims to employ three-dimensional (3D) microphysiological models such as an induced pluripotent stem cells–derived mini-brain model from our laboratory. These complex models have to be complemented with, favorably 3D, models of homogenous cell models for pathway identification; an example of a 3D dopaminergic neurons (LUHMES) model is given. The human mini-brain model offers opportunities beyond studying developmental effects. It is also undergoing further amendments such as the addition of microglia and a blood–brain barrier. A major recent breakthrough showed that the model could be frozen for stockpiling and transport. This enables us to make the model readily available via commercial vendors. For this purpose, a Johns Hopkins spin-off biotech company, Organome LLC, was formed.</dcterms:abstract>
    <dcterms:title>Human 3D In Vitro Models for Developmental Neurotoxicity</dcterms:title>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
  </rdf:Description>
</rdf:RDF>

Bibliography of Konstanz

Yes