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ResearchIn-Press PreviewMuscle biologyStem cells Open Access | 10.1172/JCI166998
1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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1Laboratory of Regenerative and Movement Biology, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
2Biozentrum, University of Basel, Basel, Switzerland
3Laboratory of Exercise and Health, ETH Zurich (Swiss Federal Institute of Technology Zurich), Schwerzenbach, Switzerland
4Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
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Published May 7, 2024 - More info
Satellite cells, the stem cells of skeletal muscle tissue, hold a remarkable regeneration capacity and therapeutic potential in regenerative medicine. However, low satellite cell yield from autologous or donor-derived muscles hinders the adoption of satellite cell transplantation for the treatment of muscle diseases, including Duchenne muscular dystrophy (DMD). To address this limitation, here we investigated whether satellite cells can be derived in allogeneic or xenogeneic animal hosts. First, injection of CRISPR/Cas9-corrected mouse DMD-induced pluripotent stem cells (iPSCs) into mouse blastocysts carrying an ablation system of host satellite cells gave rise to intraspecies chimeras exclusively carrying iPSC-derived satellite cells. Furthermore, injection of genetically corrected DMD-iPSCs into rat blastocysts resulted in the formation of interspecies rat-mouse chimeras harboring mouse satellite cells. Remarkably, iPSC-derived satellite cells or derivative myoblasts produced in intraspecies or interspecies chimeras restored dystrophin expression in DMD mice following intramuscular transplantation, and contributed to the satellite cell pool. Collectively, this study demonstrates the feasibility of producing therapeutically competent stem cells across divergent animal species, raising the possibility of generating human muscle stem cells in large animals for regenerative medicine purposes.
View Unedited blot and gel images
View Supporting scRNA-Seq data
View Supplemental video 2: CreERT2xDTA chimera myotubes
View Supplemental video 4: Rat mouse chimera myotubes
View Supplemental video 5: Re-isolated myotubes
View Supplemental video 3: CrexDTA chimera myotubes