In vitro chronic neurotoxicity assays: present and future developments

D.A. Nagel*, E.J. Hill, M.D. Coleman

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

With growing regulatory emphasis on the evaluation of increasing numbers of possible neurotoxins in the environment, as well as for novel therapeutic agent testing, the need for relevant, high-throughput and human-based in vitro neurotoxicity assays has never been greater. Although current in vitro human neurotoxicity models, such as neuroblastoma or glial cell lines and primary cells, are not adequate models for human predictive neurotoxicity, the NT.2D1 line, derived from a human teratoma, can be differentiated into functional cocultures of human neurons and astrocytes, which is the model that is the closest representation of living human neuronal and astrocytic capability that can be sustained in vitro. As acute neurotoxicity assays and developmental three-dimensional neurosphere assays have already been established with this model and with appropriate endpoints, there is no reason why increasingly sophisticated chronic models of neurotoxicity lasting in excess of 90 days cannot be devised using these cells. It is anticipated that current innovations such as perfused microbioreactors and blood-brain barrier models combined with the NT2.D1 line will improve cellular yields, accelerate differentiation durations, and increase functionality and relevance to man, in order to develop advanced and highly predictive chronic neurotoxicity systems in the future.

Original languageEnglish
Title of host publicationMedical biotechnology and healthcare
EditorsMurray Moo-Young
PublisherAcademic Press
Pages573-585
Number of pages13
Volume5
Edition2nd
ISBN (Electronic)978-0-08-088504-9
ISBN (Print)978-0-444-53352-4
DOIs
Publication statusPublished - 2011

Keywords

  • bioreactor
  • differentiation
  • human
  • neurotoxicity
  • NT2.D1

Fingerprint Dive into the research topics of 'In vitro chronic neurotoxicity assays: present and future developments'. Together they form a unique fingerprint.

  • Cite this

    Nagel, D. A., Hill, E. J., & Coleman, M. D. (2011). In vitro chronic neurotoxicity assays: present and future developments. In M. Moo-Young (Ed.), Medical biotechnology and healthcare (2nd ed., Vol. 5, pp. 573-585). Academic Press. https://doi.org/10.1016/B978-0-08-088504-9.00514-6