Neuromuscular junction
AssigneeCedars-Sinai Medical Center
InventorsDhruv Sareen, Berhan Mandefro, Anjoscha Kaus
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Abstract
The invention relates to culturing motor neuron cells together with skeletal muscle cells in a fluidic device under conditions whereby the interaction of these cells mimic the structure and function of the neuromuscular junction (NMJ) providing a NMJ-on-chip. Good viability, formation of myo-fibers and function of skeletal muscle cells on fluidic chips allow for measurements of muscle cell contractions. Embodiments of motor neurons co-cultures with contractile myo-fibers are contemplated for use with modeling diseases affecting NMJ's, e.g. Amyotrophic lateral sclerosis (ALS).
Claims16
A neuromuscular junction generated on a microfluidic device (NMJ-on-chip) comprising:
- one or more human induced pluripotent stem cell (iPSC)-derived neurons seeded into an upper channel or a lower channel of the microfluidic device;
- and
- one or more human iPSC-derived muscle cells seeded into the upper channel or the lower channel of the microfluidic device, wherein the one or more human iPSC-derived muscles cells are not in the same channel as the one or more human iPSC-derived neurons,
- wherein the one or more neurons are capable of generating a nerve action potential and inducing spontaneous contraction in the one or more muscle cells,
- wherein the microfluidic device comprises a culture media including Compound E, DAPT, db-cAMP, Ascorbic Acid, Glial cell-derived neurotrophic factor (GDNF), Brain-derived neurotrophic factor (BDNF), and VPA (valproic acid), and
- wherein the culture media lowers spontaneous contraction rates of myofibers or myotube formed from the one or more muscle cells, the myofibers or myotube growing on top of a membrane of the NMJ-on-chip, and the membrane separating the upper channel and the lower channel.
Dependencies are inferred from the claim text.