{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:31:46Z","timestamp":1790112706200,"version":"4.0.1"},"reference-count":95,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, marked by progressive degeneration of upper and lower motor neurons. Clinically, genetically, and pathologically heterogeneous, ALS poses a major challenge for disease modeling and therapeutic translation. Over the past two decades, induced pluripotent stem cells (iPSCs) have reshaped our understanding of ALS pathogenesis and emerged as a promising translational platform for therapy development. ALS modeling has further expanded with the advent of three-dimensional systems, including ALS-on-chip platforms and organoid models, which better capture cell\u2013cell interactions and tissue-level phenotypes. Despite these advances, effective disease-modifying therapies remain elusive. Recent clinical trial setbacks highlight the need for improved trial design alongside robust, translational iPSC models that can better predict therapeutic response. Nonetheless, the outlook is promising as large iPSC patient cohorts, quantitative phenotyping combined with genetically informed patient stratification, and reverse translational research are beginning to close the gap between in vitro discovery and clinical testing. In this review, we summarize the major advances in iPSC technology and highlight key iPSC-based studies of sporadic ALS. We further discuss emerging examples of iPSC-informed therapeutic strategies and outline the challenges associated with translating iPSC-derived mechanistic insights and pharmacological findings into successful clinical therapies.<\/jats:p>","DOI":"10.3390\/cells15030247","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:41:56Z","timestamp":1769528516000},"page":"247","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Dish to Trial: Building Translational Models of ALS"],"prefix":"10.3390","volume":"15","author":[{"given":"Ilias","family":"Salamotas","sequence":"first","affiliation":[{"name":"Laboratory of Neurodegenerative Disease, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9529-5324","authenticated-orcid":false,"given":"Sotiria","family":"Stavropoulou De Lorenzo","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disease, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aggeliki","family":"Stachtiari","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disease, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2137-715X","authenticated-orcid":false,"given":"Apostolos","family":"Taxiarchis","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Chemistry, Karolinska University Laboratory, Karolinska University Hospital, 17166 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2072-8010","authenticated-orcid":false,"given":"Magda","family":"Tsolaki","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disease, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iliana","family":"Michailidou","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disease, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece"},{"name":"Division of Science and Technology, Anatolia American University, Pylaia, 55535 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-4621","authenticated-orcid":false,"given":"Elisavet","family":"Preza","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disease, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Park, J., Kim, J.-E., and Song, T.-J. 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