{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:58:53Z","timestamp":1790848733711,"version":"4.1.0"},"reference-count":192,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015550","name":"Ministry of Health","doi-asserted-by":"publisher","award":["JPND2022-DC4MND"],"award-info":[{"award-number":["JPND2022-DC4MND"]}],"id":[{"id":"10.13039\/501100015550","id-type":"DOI","asserted-by":"publisher"}]},{"award":["JPND2022-DC4MND"],"award-info":[{"award-number":["JPND2022-DC4MND"]}],"id":[{"id":"https:\/\/ror.org\/00789fa95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Induced pluripotent stem cells (iPSCs) have revolutionized disease modelling by providing unprecedented opportunities to investigate complex human disorders. Among others, Amyotrophic Lateral Sclerosis (ALS), the most common adult-onset motor neuron disease, clearly embodies this complexity. This disorder remains particularly challenging not only because of its marked clinical and molecular heterogeneity but also as a consequence of the composite interactions between motor neurons and the neighboring non-neuronal cells, especially astrocytes, which contribute to disease progression. The ability to generate patient-specific spinal motor neurons and astrocytes from human iPSCs has enabled the development of in vitro models that recapitulate key pathological features of ALS, offering valuable platforms to investigate disease mechanisms, to identify therapeutic targets, and to support personalized medicine approaches. In this review, we summarize current iPSC-based strategies for modelling ALS, highlighting their applications in studying disease physiopathology and drug development. In addition, advanced human iPSC-derived technologies, including organoids and organ-on-a-chip systems, are discussed highlighting their potential, current limitations, and future perspectives.<\/jats:p>","DOI":"10.3390\/cells15191798","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:38:16Z","timestamp":1790847496000},"page":"1798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Motor Neuron Disease in a Dish: The Power of Human Induced Pluripotent Stem Cell-Derived Spinal Motor Neurons and Glial Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Martina","family":"Morrone","sequence":"first","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Laboratory for Research on Neurodegenerative Disorders, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5993-6522","authenticated-orcid":false,"given":"Chiara F.","family":"Valori","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Laboratory for Research on Neurodegenerative Disorders, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5714-3625","authenticated-orcid":false,"given":"Liliana","family":"Brambilla","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Laboratory for Research on Neurodegenerative Disorders, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-1327","authenticated-orcid":false,"given":"Daniela","family":"Rossi","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Laboratory for Research on Neurodegenerative Disorders, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.stem.2020.09.014","article-title":"Pluripotent Stem Cell-Based Cell Therapy-Promise and Challenges","volume":"27","author":"Yamanaka","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/nn.2577","article-title":"What can pluripotent stem cells teach us about neurodegenerative diseases?","volume":"13","author":"Wichterle","year":"2010","journal-title":"Nat. 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