Human-Relevant Sensitivity of iPSC-Derived Human Motor Neurons to BoNT/A1 and B1.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractThe application of botulinum neurotoxins (BoNTs) for medical treatments necessitates a potency quantification of these lethal bacterial toxins, resulting in the use of a large number of test animals. Available alternative methods are limited in their relevance, as they are based on rodent cells or neuroblastoma cell lines or applicable for single toxin serotypes only. Here, human motor neurons (MNs), which are the physiological target of BoNTs, were generated from induced pluripotent stem cells (iPSCs) and compared to the neuroblastoma cell line SiMa, which is often used in cell-based assays for BoNT potency determination. In comparison with the mouse bioassay, human MNs exhibit a superior sensitivity to the BoNT serotypes A1 and B1 at levels that are reflective of human sensitivity. SiMa cells were able to detect BoNT/A1, but with much lower sensitivity than human MNs and appear unsuitable to detect any BoNT/B1 activity. The MNs used for these experiments were generated according to three differentiation protocols, which resulted in distinct sensitivity levels. Molecular parameters such as receptor protein concentration and electrical activity of the MNs were analyzed, but are not predictive for BoNT sensitivity. These results show that human MNs from several sources should be considered in BoNT testing and that human MNs are a physiologically relevant model, which could be used to optimize current BoNT potency testing.
CitationToxins (Basel). 2021 Aug 22;13(8):585. doi: 10.3390/toxins13080585.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
- Analysis of Motor Neurons Differentiated from Human Induced Pluripotent Stem Cells for the Use in Cell-Based Botulinum Neurotoxin Activity Assays.
- Authors: Schenke M, Schjeide BM, Püschel GP, Seeger B
- Issue date: 2020 Apr 25
- Isolation and Characterization of the Novel Botulinum Neurotoxin A Subtype 6.
- Authors: Moritz MS, Tepp WH, Bradshaw M, Johnson EA, Pellett S
- Issue date: 2018 Oct 24
- Purification and Characterization of Botulinum Neurotoxin FA from a Genetically Modified Clostridium botulinum Strain.
- Authors: Pellett S, Tepp WH, Bradshaw M, Kalb SR, Dykes JK, Lin G, Nawrocki EM, Pier CL, Barr JR, Maslanka SE, Johnson EA
- Issue date: 2016 Jan-Feb
- Assessment of ELISA as endpoint in neuronal cell-based assay for BoNT detection using hiPSC derived neurons.
- Authors: Pellett S, Tepp WH, Johnson EA, Sesardic D
- Issue date: 2017 Nov
- hiPSC-Derived Neurons Provide a Robust and Physiologically Relevant <i>In Vitro</i> Platform to Test Botulinum Neurotoxins.
- Authors: Lamotte JD, Roqueviere S, Gautier H, Raban E, Bouré C, Fonfria E, Krupp J, Nicoleau C
- Issue date: 2020