Universität zu Köln

Hoelting, Lisa, Klima, Stefanie, Karreman, Christiaan, Grinberg, Marianna, Meisig, Johannes, Henry, Margit, Rotshteyn, Tamara, Rahnenfuehrer, Joerg, Bluethgen, Nils, Sachinidis, Agapios, Waldmann, Tanja and Leist, Marcel ORCID: 0000-0002-3778-8693 (2016). Stem Cell-Derived Immature Human Dorsal Root Ganglia Neurons to Identify Peripheral Neurotoxicants. Stem Cells Transl. Med., 5 (4). S. 476 - 488. HOBOKEN: WILEY. ISSN 2157-6580

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Abstract

Safety sciences and the identification of chemical hazards have been seen as one of the most immediate practical applications of human pluripotent stem cell technology. Protocols for the generation of many desirable human cell types have been developed, but optimization of neuronal models for toxicological use has been astonishingly slow, and the wide, clinically important field of peripheral neurotoxicity is still largely unexplored. A two-step protocol to generate large lots of identical peripheral human neuronal precursors was characterized and adapted to the measurement of peripheral neurotoxicity. High content imaging allowed an unbiased assessment of cell morphology and viability. The computational quantification of neurite growth as a functional parameter highly sensitive to disturbances by toxicants was used as an endpoint reflecting specific neurotoxicity. The differentiation of cells toward dorsal root ganglia neurons was tracked in relation to a large background data set based on gene expression microarrays. On this basis, a peripheral neurotoxicity (PeriTox) test was developed as a first toxicological assay that harnesses the potential of human pluripotent stem cells to generate cell types/tissues that are not otherwise available for the prediction of human systemic organ toxicity. Testing of more than 30 chemicals showed that human neurotoxicants and neurite growth enhancers were correctly identified. Various classes of chemotherapeutic agents causing human peripheral neuropathies were identified, and they were missed when tested on human central neurons. The PeriTox test we established shows the potential of human stem cells for clinically relevant safety testing of drugs in use and of new emerging candidates.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hoelting, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Klima, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Karreman, Christiaan UNSPECIFIED UNSPECIFIED UNSPECIFIED Grinberg, Marianna UNSPECIFIED UNSPECIFIED UNSPECIFIED Meisig, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Henry, Margit UNSPECIFIED UNSPECIFIED UNSPECIFIED Rotshteyn, Tamara UNSPECIFIED UNSPECIFIED UNSPECIFIED Rahnenfuehrer, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Bluethgen, Nils UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Waldmann, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Leist, Marcel UNSPECIFIED orcid.org/0000-0002-3778-8693 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-280758
DOI:	10.5966/sctm.2015-0108
Journal or Publication Title:	Stem Cells Transl. Med.
Volume:	5
Number:	4
Page Range:	S. 476 - 488
Date:	2016
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2157-6580
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DEVELOPMENTAL NEUROTOXICITY; IN-VITRO; NEURITE OUTGROWTH; GENE-EXPRESSION; NEUROPATHY; PROTECTION; TOXICOLOGY; CULTURES; DEGENERATION; PREVALENCE Multiple languages Cell & Tissue Engineering Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28075