Tissue-engineered neuromuscular organoids
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.
Authors
- Onelia Gagliano (ORCID: https://orcid.org/0000-0002-2571-3176)
- Yvan Torrente (ORCID: https://orcid.org/0000-0002-2705-3984)
- Maria Easler (ORCID: https://orcid.org/0000-0002-9596-6005)
- Davide Cacchiarelli (ORCID: https://orcid.org/0000-0002-9621-6716)
- Chiara Villa (ORCID: https://orcid.org/0000-0002-3002-3372)
- Nicola Elvassore (ORCID: https://orcid.org/0000-0002-7029-6287)
- Camilla Luni (ORCID: https://orcid.org/0000-0002-1211-9629)
- Sonia Calabrò (ORCID: https://orcid.org/0009-0006-9146-1508)
- Martina Piccoli (ORCID: https://orcid.org/0000-0001-6211-0051)
- Beatrice Auletta (ORCID: https://orcid.org/0009-0003-2237-6690)
- Paolo Raffa (ORCID: https://orcid.org/0000-0003-0370-6108)
- Cecilia Laterza (ORCID: https://orcid.org/0000-0002-3964-3375)
- Matilde Cescon (ORCID: https://orcid.org/0000-0001-7138-1857)
- Lucia Rossi (ORCID: https://orcid.org/0009-0000-1703-1354)
- Leonardo Sartore
- Anna Urciuolo
- Monica Giomo (ORCID: https://orcid.org/0000-0002-7690-1054)
- Francesca Cecchinato
- Silvia Angiolillo (ORCID: https://orcid.org/0000-0001-5589-4177)
- Edoardo Maghin (ORCID: https://orcid.org/0000-0002-1479-0221)
- Agnese Lauroja
- Pietro Chiolerio (ORCID: https://orcid.org/0000-0002-1717-2082)
- Giada Cecconi
- Wei Qin (ORCID: https://orcid.org/0009-0007-4061-2326)
- Gilda Barbato
- Roberta Frison
Institutions
- University of Padua (IT)
- University of Milan (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Veneto Institute of Molecular Medicine (IT)
- Scuola Superiore Meridionale (IT)
- Telethon Institute Of Genetics And Medicine (IT)
- Città della Speranza Foundation (IT)
- University of Naples Federico II (IT)
- University of Bologna (IT)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-07-19
- DOI
- https://doi.org/10.1038/s42003-025-08484-z
- Citations
- 4
- Primary Topic
- Tissue Engineering and Regenerative Medicine
- Type
- article
- Field-Weighted Citation Impact
- 8.03