{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:07:39Z","timestamp":1790842059261,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013465","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["20987"],"award-info":[{"award-number":["20987"]}],"id":[{"id":"10.13039\/100013465","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["20CVD04"],"award-info":[{"award-number":["20CVD04"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["MBExC 2067"],"award-info":[{"award-number":["MBExC 2067"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["IRTG 1816"],"award-info":[{"award-number":["IRTG 1816"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG SFB 1002 C04\/S01"],"award-info":[{"award-number":["DFG SFB 1002 C04\/S01"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFGTI956\/1\u20101"],"award-info":[{"award-number":["DFGTI956\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010447","name":"Deutsches Zentrum f\u00fcr Herz-Kreislaufforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Human pluripotent stem cell\u2010derived muscle models show great potential for translational research. Here, we describe developmentally inspired methods for the derivation of skeletal muscle cells and their utility in skeletal muscle tissue engineering with the aim to model skeletal muscle regeneration and dystrophy in vitro.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Key steps include the directed differentiation of human pluripotent stem cells to embryonic muscle progenitors followed by primary and secondary foetal myogenesis into three\u2010dimensional muscle. To simulate Duchenne muscular dystrophy (DMD), a patient\u2010specific induced pluripotent stem cell line was compared to a CRISPR\/Cas9\u2010edited isogenic control line.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The established skeletal muscle differentiation protocol robustly and faithfully recapitulates critical steps of embryonic myogenesis in two\u2010dimensional and three\u2010dimensional cultures, resulting in functional human skeletal muscle organoids (SMOs) and engineered skeletal muscles (ESMs) with a regeneration\u2010competent satellite\u2010like cell pool. Tissue\u2010engineered muscle exhibits organotypic maturation and function (up to 5.7\u00a0\u00b1\u00a00.5\u00a0mN tetanic twitch tension at 100\u00a0Hz in ESM). Contractile performance could be further enhanced by timed thyroid hormone treatment, increasing the speed of contraction (time to peak contraction) as well as relaxation (time to 50% relaxation) of single twitches from 107\u00a0\u00b1\u00a02 to 75\u00a0\u00b1\u00a04\u00a0ms (\n P<\/jats:italic>\n \u00a0<\u00a00.05) and from 146\u00a0\u00b1\u00a06 to 100\u00a0\u00b1\u00a06\u00a0ms (\n P<\/jats:italic>\n \u00a0<\u00a00.05), respectively. Satellite\u2010like cells could be documented as largely quiescent PAX7\n +<\/jats:sup>\n cells (75\u00a0\u00b1\u00a06% Ki67\n \u2212<\/jats:sup>\n ) located adjacent to muscle fibres confined under a laminin\u2010containing basal membrane. Activation of the engineered satellite\u2010like cell niche was documented in a cardiotoxin injury model with marked recovery of contractility to 57\u00a0\u00b1\u00a08% of the pre\u2010injury force 21\u00a0days post\u2010injury (\n P<\/jats:italic>\n \u00a0<\u00a00.05 compared to Day 2 post\u2010injury), which was completely blocked by preceding irradiation. Absence of dystrophin in DMD ESM caused a marked reduction of contractile force (\u221235\u00a0\u00b1\u00a07%,\n P<\/jats:italic>\n \u00a0<\u00a00.05) and impaired expression of fast myosin isoforms resulting in prolonged contraction (175\u00a0\u00b1\u00a014\u00a0ms,\n P<\/jats:italic>\n \u00a0<\u00a00.05 vs. gene\u2010edited control) and relaxation (238\u00a0\u00b1\u00a022\u00a0ms,\n P<\/jats:italic>\n \u00a0<\u00a00.05 vs. gene\u2010edited control) times. Restoration of dystrophin levels by gene editing rescued the DMD phenotype in ESM.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n We introduce human muscle models with canonical properties of bona fide skeletal muscle in vivo to study muscle development, maturation, disease and repair.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.13094","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T05:37:41Z","timestamp":1666071461000},"page":"3106-3121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Engineered skeletal muscle recapitulates human muscle development, regeneration and dystrophy"],"prefix":"10.1002","volume":"13","author":[{"given":"Mina","family":"Shahriyari","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology University Medical Center G\u00f6ttingen, Georg August University G\u00f6ttingen Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), partner site G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Rezaul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases German Center for Neurodegenerative Diseases (DZNE) G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadman M.","family":"Sakib","sequence":"additional","affiliation":[{"name":"Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases German Center for Neurodegenerative Diseases (DZNE) G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Rinn","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University Medical Center G\u00f6ttingen, Georg August University G\u00f6ttingen Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), partner site G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Rika","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University Medical Center G\u00f6ttingen, Georg August University G\u00f6ttingen Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), partner site G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases German Center for Neurodegenerative Diseases (DZNE) G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalit","family":"Kaurani","sequence":"additional","affiliation":[{"name":"Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases 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Wellstone Muscular Dystrophy Cooperative Research Center University of Texas Southwestern Medical Center Dallas TX USA"},{"name":"Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric N.","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology University of Texas Southwestern Medical Center Dallas TX USA"},{"name":"Senator Paul D. 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