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<p>Skeletal muscle development, homeostasis, and function rely on complex interactions among multiple cell types and the extracellular matrix (ECM). Developing in vitro models that recapitulate both intrinsic cellular and extrinsic ECM elements of innervated skeletal muscle is crucial for advancing basic biology and disease modeling studies. Here, we combine tissue engineering approaches with human induced pluripotent stem cell (hiPSC) technology to create tissue-engineered neuromuscular organoids (t-NMOs). Using decellularized muscles as scaffolds, hiPSCs differentiate to form organoids that establish a continuum with the provided biomaterial. After 30 days, t-NMOs exhibit compartmentalized neural and muscular components that establish functional interactions, allowing muscle contraction. We demonstrate the model’s potential by creating Duchenne Muscular Dystrophy&#xa0;patient-specific t-NMOs, that recapitulate the reduced skeletal muscle contraction and altered calcium dynamics typical of the disease. Altogether, our study presents a tissue-engineered organoid that&#xa0;model the human neuromuscular system (dys)function, highlighting the potential of applying&#xa0;the ECM in organoid engineering.</p><p></p>

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Tissue-engineered neuromuscular organoids

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月19日

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  • Beatrice Auletta,
  • Pietro Chiolerio,
  • Giada Cecconi,
  • Lucia Rossi,
  • Luigi Sartore,
  • Francesca Cecchinato,
  • Gilda Barbato,
  • Agnese Lauroja,
  • Edoardo Maghin,
  • Maria Easler,
  • Paolo Raffa,
  • Silvia Angiolillo,
  • Wei Qin,
  • Roberta Frison,
  • Sonia Calabrò,
  • Chiara Villa,
  • Onelia Gagliano,
  • Cecilia Laterza,
  • Davide Cacchiarelli,
  • Matilde Cescon,
  • Monica Giomo,
  • Yvan Torrente,
  • Camilla Luni,
  • Martina Piccoli,
  • Nicola Elvassore,
  • Anna Urciuolo

摘要

Skeletal muscle development, homeostasis, and function rely on complex interactions among multiple cell types and the extracellular matrix (ECM). Developing in vitro models that recapitulate both intrinsic cellular and extrinsic ECM elements of innervated skeletal muscle is crucial for advancing basic biology and disease modeling studies. Here, we combine tissue engineering approaches with human induced pluripotent stem cell (hiPSC) technology to create tissue-engineered neuromuscular organoids (t-NMOs). Using decellularized muscles as scaffolds, hiPSCs differentiate to form organoids that establish a continuum with the provided biomaterial. After 30 days, t-NMOs exhibit compartmentalized neural and muscular components that establish functional interactions, allowing muscle contraction. We demonstrate the model’s potential by creating Duchenne Muscular Dystrophy patient-specific t-NMOs, that recapitulate the reduced skeletal muscle contraction and altered calcium dynamics typical of the disease. Altogether, our study presents a tissue-engineered organoid that model the human neuromuscular system (dys)function, highlighting the potential of applying the ECM in organoid engineering.