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Analysis of Motor Neurons Differentiated from Human Induced Pluripotent Stem Cells for the Use in Cell-Based Botulinum Neurotoxin Activity Assays

1
Institute for Food Toxicology, Department of Food Toxicology and Replacement/Complementary Methods to Animal Testing, University of Veterinary Medicine, 30173 Hannover, Germany
2
Institute of Nutritional Science, Department of Nutritional Biochemistry, University of Potsdam, 14558 Nuthetal, Germany
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(5), 276; https://doi.org/10.3390/toxins12050276
Received: 12 February 2020 / Revised: 12 April 2020 / Accepted: 23 April 2020 / Published: 25 April 2020
(This article belongs to the Section Bacterial Toxins)
Botulinum neurotoxins (BoNTs) are potent neurotoxins produced by bacteria, which inhibit neurotransmitter release, specifically in their physiological target known as motor neurons (MNs). For the potency assessment of BoNTs produced for treatment in traditional and aesthetic medicine, the mouse lethality assay is still used by the majority of manufacturers, which is ethically questionable in terms of the 3Rs principle. In this study, MNs were differentiated from human induced pluripotent stem cells based on three published protocols. The resulting cell populations were analyzed for their MN yield and their suitability for the potency assessment of BoNTs. MNs produce specific gangliosides and synaptic proteins, which are bound by BoNTs in order to be taken up by receptor-mediated endocytosis, which is followed by cleavage of specific soluble N-ethylmaleimide-sensitive-factor attachment receptor (SNARE) proteins required for neurotransmitter release. The presence of receptors and substrates for all BoNT serotypes was demonstrated in MNs generated in vitro. In particular, the MN differentiation protocol based on Du et al. yielded high numbers of MNs in a short amount of time with high expression of BoNT receptors and targets. The resulting cells are more sensitive to BoNT/A1 than the commonly used neuroblastoma cell line SiMa. MNs are, therefore, an ideal tool for being combined with already established detection methods. View Full-Text
Keywords: Botulinum neurotoxin; motor neurons; cell-based in vitro assay; potency assessment; induced pluripotent stem cells Botulinum neurotoxin; motor neurons; cell-based in vitro assay; potency assessment; induced pluripotent stem cells
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MDPI and ACS Style

Schenke, M.; Schjeide, B.-M.; Püschel, G.P.; Seeger, B. Analysis of Motor Neurons Differentiated from Human Induced Pluripotent Stem Cells for the Use in Cell-Based Botulinum Neurotoxin Activity Assays. Toxins 2020, 12, 276. https://doi.org/10.3390/toxins12050276

AMA Style

Schenke M, Schjeide B-M, Püschel GP, Seeger B. Analysis of Motor Neurons Differentiated from Human Induced Pluripotent Stem Cells for the Use in Cell-Based Botulinum Neurotoxin Activity Assays. Toxins. 2020; 12(5):276. https://doi.org/10.3390/toxins12050276

Chicago/Turabian Style

Schenke, Maren; Schjeide, Brit-Maren; Püschel, Gerhard P.; Seeger, Bettina. 2020. "Analysis of Motor Neurons Differentiated from Human Induced Pluripotent Stem Cells for the Use in Cell-Based Botulinum Neurotoxin Activity Assays" Toxins 12, no. 5: 276. https://doi.org/10.3390/toxins12050276

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