A scalable human iPSC-based neuromuscular disease model on suspended biobased elastomer nanofiber scaffolds.
CRISPR-Cas9
amyotrophic lateral sclerosis
biobased elastomer nanofibers
high content image analysis
human induced pluripotent stem cells
optogenetics
scalable neuromuscular disease modelling
Journal
Biofabrication
ISSN: 1758-5090
Titre abrégé: Biofabrication
Pays: England
ID NLM: 101521964
Informations de publication
Date de publication:
05 09 2023
05 09 2023
Historique:
received:
02
03
2023
accepted:
24
08
2023
medline:
6
9
2023
pubmed:
25
8
2023
entrez:
24
8
2023
Statut:
epublish
Résumé
Many devastating neuromuscular diseases currently lack effective treatments. This is in part due to a lack of drug discovery platforms capable of assessing complex human neuromuscular disease phenotypes in a scalable manner. A major obstacle has been generating scaffolds to stabilise mature contractile myofibers in a multi-well assay format amenable to high content image (HCI) analysis. This study describes the development of a scalable human induced pluripotent stem cell (iPSC)-neuromuscular disease model, whereby suspended elastomer nanofibers support long-term stability, alignment, maturation, and repeated contractions of iPSC-myofibers, innervated by iPSC-motor neurons in 96-well assay plates. In this platform, optogenetic stimulation of the motor neurons elicits robust myofiber-contractions, providing a functional readout of neuromuscular transmission. Additionally, HCI analysis provides rapid and automated quantification of axonal outgrowth, myofiber morphology, and neuromuscular synapse number and morphology. By incorporating amyotrophic lateral sclerosis (ALS)-related TDP-43
Identifiants
pubmed: 37619554
doi: 10.1088/1758-5090/acf39e
pmc: PMC10478173
doi:
Substances chimiques
Elastomers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M009513/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N025865/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 108874/Z/15/Z
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT098503
Pays : United Kingdom
Informations de copyright
Creative Commons Attribution license.
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