Tissue-engineered neuromuscular organoids.

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Neuroscience

Background:

• Skeletal muscle function depends on intricate cell and extracellular matrix (ECM) interactions.
• In vitro models are needed to study innervated skeletal muscle's cellular and ECM components.

Purpose of the Study:

• To engineer functional human neuromuscular organoids using decellularized muscle scaffolds and human induced pluripotent stem cells (hiPSCs).
• To create a model for studying neuromuscular system development, homeostasis, and disease.

Main Methods:

• Utilized decellularized muscle tissue as a scaffold for hiPSC differentiation.
• Developed tissue-engineered neuromuscular organoids (t-NMOs) over 30 days.
• Created patient-specific t-NMOs from individuals with Duchenne Muscular Dystrophy.

Main Results:

• t-NMOs exhibited compartmentalized neural and muscular tissues with functional interactions and muscle contraction.
• Patient-specific t-NMOs recapitulated reduced muscle contraction and altered calcium dynamics characteristic of Duchenne Muscular Dystrophy.
• Demonstrated the potential of ECM in organoid engineering for modeling neuromuscular function and dysfunction.

Conclusions:

• The study presents a novel tissue-engineered organoid model of the human neuromuscular system.
• This model successfully recapitulates neuromuscular system (dys)function, including disease-specific phenotypes.
• Highlights the utility of ECM-based scaffolds in creating advanced organoid models for biomedical research.