Aberrant axon initial segment plasticity and intrinsic excitability of ALS hiPSC motor neurons.

Dysregulated neuronal excitability is a hallmark of amyotrophic lateral sclerosis (ALS). We sought to investigate how functional changes to the axon initial segment (AIS), the site of action potential generation, could impact neuronal excitability in ALS human induced pluripotent stem cell (hiPSC) motor neurons. We find that early TDP-43 and C9orf72 hiPSC motor neurons show an increase in the length of the AIS and impaired activity-dependent AIS plasticity that is linked to abnormal homeostatic regulation of neuronal activity and intrinsic hyperexcitability.

A scalable human iPSC-based neuromuscular disease model on suspended biobased elastomer nanofiber scaffolds.

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.

Biobased Elastomer Nanofibers Guide Light-Controlled Human-iPSC-Derived Skeletal Myofibers.

Generating skeletal muscle tissue that mimics the cellular alignment, maturation, and function of native skeletal muscle is an ongoing challenge in disease modeling and regenerative therapies. Skeletal muscle cultures require extracellular guidance and mechanical support to stabilize contractile myofibers. Existing microfabrication-based solutions are limited by complex fabrication steps, low throughput, and challenges in measuring dynamic contractile function.