Highly contractile 3D tissue engineered skeletal muscles from human iPSCs reveal similarities with primary myoblast-derived tissues
Stem Cell Reports, vol. 18, pp. 1954–1971
Abstract
Skeletal muscle research is transitioning toward 3D tissue engineered in vitro models reproducing muscle's native architecture and supporting measurement of functionality. Human induced pluripotent stem cells (hiPSCs) offer high yields of cells for differentiation. It has been difficult to differentiate high-quality, pure 3D muscle tissues from hiPSCs that show contractile properties comparable to primary myoblast-derived tissues. Here, we present a transgene-free method for the generation of purified, expandable myogenic progenitors (MPs) from hiPSCs grown under feeder-free conditions. We defined a protocol with optimal hydrogel and medium conditions that allowed production of highly contractile 3D tissue engineered skeletal muscles with forces similar to primary myoblast-derived tissues. Gene expression and proteomic analysis between hiPSC-derived and primary myoblast-derived 3D tissues revealed a similar expression profile of proteins involved in myogenic differentiation and sarcomere function. The protocol should be generally applicable for the study of personalized human skeletal muscle tissue in health and disease.
Authors 11
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Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
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Erasmus MC · Erasmus University Rotterdam
Affiliation as printed
Department of Clinical Genetics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands; Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
Department of Clinical Genetics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
Department of Pediatrics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
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Erasmus MC · Erasmus University Rotterdam
Affiliation as printed
Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
Department of Clinical Genetics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
Department of Pediatrics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
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Erasmus MC · Erasmus University Rotterdam
Affiliation as printed
Department of Clinical Genetics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands; Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
Department of Clinical Genetics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
Department of Pediatrics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
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University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
Affiliation as printed
Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Center for Molecular Medicine, University of Cologne, Cologne, Germany
Center for Molecular Medicine, University of Cologne, Cologne, Germany
Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
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Wageningen University & Research
Affiliation as printed
Physical Chemistry and Soft Matter, Wageningen University and Research, 6708 WE Wageningen, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
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Wageningen University & Research
Affiliation as printed
Department of BioNanoTechnology, Wageningen University and Research, 6708 WG Wageningen, the Netherlands
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University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
Affiliation as printed
Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Center for Molecular Medicine, University of Cologne, Cologne, Germany
Center for Molecular Medicine, University of Cologne, Cologne, Germany
Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
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W.W.M. Pim Pijnappel corresponding
Erasmus MC · Erasmus University Rotterdam
Affiliation as printed
Department of Clinical Genetics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands; Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands. Electronic address: w.pijnappel@erasmusmc.nl
Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
Department of Clinical Genetics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
Department of Pediatrics, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands. Electronic address: j.c.de_greef@lumc.nl
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
Cited by 41 stored of 42
Cited by patents worldwide 1 (Lens.org)
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3D-TISSUE-ENGINEERED DISEASE MODELS AND USES THEREOFWO2025101068A1 2025-05-15 Pending