Highlights
– Turnkey iPSC-based model of the NMJ with standardized hardware-software ecosystem.
– Dose dependent loss of function with botulinum toxin application for toxin potency.
– In vivo-like staining for key pre- and postsynaptic markers.
– Demonstrated wash-in and wash-out sensitivity to fast acting neurotoxins.
Originally Published in: Science Direct (January 2025) (Link to Original Posting)
Read MoreData from Tenaya Therapeutics (2022)
Read MoreData from Entrada Therapeutics (2024)
Read MoreSummary: This protocol provides methods for generating 3D engineered cardiac and skeletal muscle tissues and describes their use in preclinical drug screening modalities. The described methods utilize a magnetic sensing system to facilitate the simultaneous assessment of 24 tissues in parallel.
Originally Published in: JoVE Journal (2023) (Link to Paper)
Read MoreAbstract: Engineered muscle tissues represent powerful tools for examining tissue level contractile properties of skeletal muscle. However, limitations in the throughput associated with standard analysis methods limit their utility for longitudinal study, high throughput drug screens, and disease modeling. Here we present a method for integrating 3D engineered skeletal muscles with a magnetic sensing system to facilitate non-invasive, longitudinal analysis of developing contraction kinetics. Using this platform, we show that engineered skeletal muscle tissues derived from both induced pluripotent stem cell and primary sources undergo improvements in contractile output over time in culture. We demonstrate how magnetic sensing of contractility can be employed for simultaneous assessment of multiple tissues subjected to different doses of known skeletal muscle inotropes as well as the stratification of healthy versus diseased functional profiles in normal and dystrophic muscle cells. Based on these data, this combined culture system and magnet-based contractility platform greatly broadens the potential for 3D engineered skeletal muscle tissues to impact the translation of novel therapies from the lab to the clinic.
Originally Published in: Sage Journals (2022) (Link to Paper)
Read More
