{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:45:25Z","timestamp":1775709925655,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T00:00:00Z","timestamp":1629590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["031L0132B"],"award-info":[{"award-number":["031L0132B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["031L0111B"],"award-info":[{"award-number":["031L0111B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The 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.<\/jats:p>","DOI":"10.3390\/toxins13080585","type":"journal-article","created":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T23:00:09Z","timestamp":1629673209000},"page":"585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Human-Relevant Sensitivity of iPSC-Derived Human Motor Neurons to BoNT\/A1 and B1"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5649-591X","authenticated-orcid":false,"given":"Maren","family":"Schenke","sequence":"first","affiliation":[{"name":"Institute for Food Quality and Safety, Research Group Food Toxicology and Alternative\/Complementary Methods to Animal Experiments, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne-Christine","family":"Prause","sequence":"additional","affiliation":[{"name":"Institute for Food Quality and Safety, Research Group Food Toxicology and Alternative\/Complementary Methods to Animal Experiments, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Germany"},{"name":"Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebke","family":"Bergforth","sequence":"additional","affiliation":[{"name":"Institute for Food Quality and Safety, Research Group Food Toxicology and Alternative\/Complementary Methods to Animal Experiments, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adina","family":"Przykopanski","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Toxikologie, Medizinische Hochschule Hannover (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0645-1641","authenticated-orcid":false,"given":"Andreas","family":"Rummel","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Toxikologie, Medizinische Hochschule Hannover (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-182X","authenticated-orcid":false,"given":"Frank","family":"Klawonn","sequence":"additional","affiliation":[{"name":"Biostatistics Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"},{"name":"Department of Computer Science, Ostfalia University, 38302 Wolfenb\u00fcttel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4653-2841","authenticated-orcid":false,"given":"Bettina","family":"Seeger","sequence":"additional","affiliation":[{"name":"Institute for Food Quality and Safety, Research Group Food Toxicology and Alternative\/Complementary Methods to Animal Experiments, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1124\/pr.116.012658","article-title":"Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology","volume":"69","author":"Pirazzini","year":"2017","journal-title":"Pharmacol. 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