Tissue-engineered neuromuscular organoids

Abstract 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 adva...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08484-z
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author 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
author_facet 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
author_sort Beatrice Auletta
collection DOAJ
description Abstract 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.
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spelling doaj-art-538fc3949c404fcc85bae17e2be6a3552025-08-20T03:46:21ZengNature PortfolioCommunications Biology2399-36422025-07-018111710.1038/s42003-025-08484-zTissue-engineered neuromuscular organoidsBeatrice Auletta0Pietro Chiolerio1Giada Cecconi2Lucia Rossi3Luigi Sartore4Francesca Cecchinato5Gilda Barbato6Agnese Lauroja7Edoardo Maghin8Maria Easler9Paolo Raffa10Silvia Angiolillo11Wei Qin12Roberta Frison13Sonia Calabrò14Chiara Villa15Onelia Gagliano16Cecilia Laterza17Davide Cacchiarelli18Matilde Cescon19Monica Giomo20Yvan Torrente21Camilla Luni22Martina Piccoli23Nicola Elvassore24Anna Urciuolo25Department of Molecular Medicine, University of PadovaDepartment of Molecular Medicine, University of PadovaDepartment of Molecular Medicine, University of PadovaDepartment of Molecular Medicine, University of PadovaDepartment of Molecular Medicine, University of PadovaDepartment of Molecular Medicine, University of PadovaNeuromuscular Engineering lab, Istituto di Ricerca Pediatrica, Città della SperanzaNeuromuscular Engineering lab, Istituto di Ricerca Pediatrica, Città della SperanzaTissue Engineering lab, Istituto di Ricerca Pediatrica, Città della SperanzaNeuromuscular Engineering lab, Istituto di Ricerca Pediatrica, Città della SperanzaNeuromuscular Engineering lab, Istituto di Ricerca Pediatrica, Città della SperanzaDepartment of Industrial Engineering, University of PadovaDepartment of Industrial Engineering, University of PadovaDepartment of Industrial Engineering, University of PadovaDepartment of Molecular Medicine, University of PadovaStem Cell Laboratory, Dino Ferrari Center, Department of Pathophysiology and Transplantation, Università di MilanoDepartment of Industrial Engineering, University of PadovaDepartment of Industrial Engineering, University of PadovaTelethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative GenomicsDepartment of Molecular Medicine, University of PadovaDepartment of Industrial Engineering, University of PadovaStem Cell Laboratory, Dino Ferrari Center, Department of Pathophysiology and Transplantation, Università di MilanoDepartment of Civil, Chemical, Environmental and Materials Engineering (DICAM), University of Bologna, Via Terracini 28Tissue Engineering lab, Istituto di Ricerca Pediatrica, Città della SperanzaDepartment of Industrial Engineering, University of PadovaDepartment of Molecular Medicine, University of PadovaAbstract 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.https://doi.org/10.1038/s42003-025-08484-z
spellingShingle 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
Tissue-engineered neuromuscular organoids
Communications Biology
title Tissue-engineered neuromuscular organoids
title_full Tissue-engineered neuromuscular organoids
title_fullStr Tissue-engineered neuromuscular organoids
title_full_unstemmed Tissue-engineered neuromuscular organoids
title_short Tissue-engineered neuromuscular organoids
title_sort tissue engineered neuromuscular organoids
url https://doi.org/10.1038/s42003-025-08484-z
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