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Innovative human preclinical models may help to uncover relevant disease mechanisms and enhance the translation of therapeutic findings to strengthen neuromuscular disease precision medicine. By concentrating on idiopathic inflammatory muscle disorders, we summarize the recent evolution of the novel in vitro models to study disease mechanisms and therapeutic strategies. A particular focus is laid on the integration and simulation of multicellular interactions of muscle tissue in disease phenotypes in vitro. Finally, the requirements of a neuromuscular disease drug development workflow are discussed with a particular emphasis on cell sources, co-culture systems (including organoids), functionality, and throughput.<\/jats:p>","DOI":"10.3390\/cells11071233","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T11:26:07Z","timestamp":1649157967000},"page":"1233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Evolution of Complex Muscle Cell In Vitro Models to Study Pathomechanisms and Drug Development of Neuromuscular Disease"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-5319","authenticated-orcid":false,"given":"Jana","family":"Zsch\u00fcntzsch","sequence":"first","affiliation":[{"name":"Department of Neurology, University Medical Center Goettingen, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Goettingen, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Shahriyari","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University Medical Center Goettingen, 37075 Goettingen, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Kummer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Goettingen, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-2932","authenticated-orcid":false,"given":"Matthias","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Goettingen, 37075 Goettingen, Germany"},{"name":"Institute of Pharmacology and Toxicology, University Medical Center Goettingen, 37075 Goettingen, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-9889","authenticated-orcid":false,"given":"Susann","family":"Kummer","sequence":"additional","affiliation":[{"name":"Risk Group 4 Pathogens\u2013Stability and Persistence, Biosafety Level-4 Laboratory, Center for Biological Threats and Special Pathogens, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6942-6275","authenticated-orcid":false,"given":"Malte","family":"Tiburcy","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University Medical Center Goettingen, 37075 Goettingen, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3233\/JND-180308","article-title":"Current Classification and Management of Inflammatory Myopathies","volume":"5","author":"Schmidt","year":"2018","journal-title":"J. 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