Jenkinson, Stephen P.; Grandgirard, Denis; Heidemann, Martina; Tscherter, Anne; Avondet, Marc-André; Leib, Stephen (2017). Embryonic Stem Cell-Derived Neurons Grown on Multi-Electrode Arrays as a Novel In vitro Bioassay for the Detection of Clostridium botulinum Neurotoxins. Frontiers in Pharmacology, 8(73) Frontiers 10.3389/fphar.2017.00073
|
Text
fphar-08-00073.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (7MB) | Preview |
Clostridium botulinum neurotoxins (BoNTs) are the most poisonous naturally occurring protein toxins known to mankind and are the causative agents of the severe and potentially life-threatening disease botulism. They are also known for their application as cosmetics and as unique bio-pharmaceuticals to treat an increasing number of neurological and non-neurological disorders. Currently, the potency of biologically active BoNT for therapeutic use is mainly monitored by the murine LD50-assay, an ethically disputable test causing suffering and death of a considerable number of mice. The aim of this study was to establish an in-vitro assay as an alternative to the widely used in-vivo mouse bioassay. We report a novel BoNT detection assay using mouse embryonic stem cell-derived neurons (mESN) cultured on multi-electrode arrays. After 21 days in culture, the mESN formed a neuronal network showing spontaneous bursting activity based on functional synapses and express the necessary target proteins for BoNTs. Treating cultures for 6 h with 16.6 pM of BoNT serotype A and incubation with 1.66 pM BoNT/A or 33 Units/ml of Botox® for 24 h lead to a significant reduction of both spontaneous network bursts and average spike rate. This data suggests that mESN cultured on multi-electrode arrays pose a novel, biologically relevant model that can be used to detect and quantify functional BoNT effects, thus accelerating BoNT research while decreasing animal use.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology 04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Grandgirard, Denis, Heidemann, Martina, Tscherter, Anne, Leib, Stephen |
Subjects: |
600 Technology > 610 Medicine & health 500 Science > 570 Life sciences; biology |
ISSN: |
1663-9812 |
Publisher: |
Frontiers |
Funders: |
[4] Swiss National Science Foundation ; [UNSPECIFIED] Swiss Federal Office for Civil Protection |
Language: |
English |
Submitter: |
Stephen Leib |
Date Deposited: |
09 Oct 2017 17:56 |
Last Modified: |
05 Dec 2022 15:03 |
Publisher DOI: |
10.3389/fphar.2017.00073 |
BORIS DOI: |
10.7892/boris.96480 |
URI: |
https://boris.unibe.ch/id/eprint/96480 |
Actions (login required)
 |
Edit item |