{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:43:34Z","timestamp":1791373414939,"version":"4.3.1"},"reference-count":154,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Science and Innovation-MICINN","award":["PID2022-137963OB-I00"],"award-info":[{"award-number":["PID2022-137963OB-I00"]}]},{"name":"Spanish Ministry of Science and Innovation-MICINN","award":["MCIN\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033"]}]},{"DOI":"10.13039\/501100003030","name":"AGAUR","doi-asserted-by":"crossref","award":["2021-SGR-974"],"award-info":[{"award-number":["2021-SGR-974"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2021-SGR-974"],"award-info":[{"award-number":["2021-SGR-974"]}],"id":[{"id":"https:\/\/ror.org\/01n4pqe45","id-type":"ROR","asserted-by":"publisher"}]},{"name":"\u201cLa Caixa\u201d Foundation","award":["HR24-00788"],"award-info":[{"award-number":["HR24-00788"]}]},{"name":"\u201cLa Caixa\u201d Foundation","award":["COMPETE2030-FEDER-00795500"],"award-info":[{"award-number":["COMPETE2030-FEDER-00795500"]}]},{"name":"\u201cLa Caixa\u201d Foundation","award":["UID\/06397\/2025"],"award-info":[{"award-number":["UID\/06397\/2025"]}]},{"DOI":"10.13039\/501100003030","name":"Agency for Management of University and Research Grants (AGAUR) of the Government of Catalonia","doi-asserted-by":"publisher","award":["2023 BP 00242"],"award-info":[{"award-number":["2023 BP 00242"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication in the brain, with glial cell-derived EVs increasingly recognized for their roles in maintaining brain homeostasis and contributing to the progression of neurodegenerative diseases. By transferring a diverse cargo of bioactive molecules, including proteins, RNAs, and organelles, EVs influence recipient cell behavior and overall brain function. In neurodegenerative conditions, glial EVs can either propagate pathogenic signals or deliver neuroprotective and regenerative cues, depending on their cellular origin and molecular composition. This context-dependent heterogeneity highlights the need for physiologically relevant human models to investigate EVs biology. Human induced pluripotent stem cell (iPSC)-derived glial models provide a disease-relevant platform, as they recapitulate key pathological features of Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD) and amyotrophic lateral sclerosis (ALS). When further integrated with brain organoid platforms, these iPSC-based systems enable the generation of three-dimensional environments that closely resemble in vivo EVs dynamics. Importantly, glial EVs can modulate cellular pathways involved in neuronal survival and function. Indeed, their potential to interact with and, under specific experimental conditions, traverse the blood\u2013brain barrier (BBB) has contributed to growing interest in their application for biomarker discovery and therapeutic development. Engineered and patient-specific EVs derived from iPSCs are emerging as promising tools for targeted, cell type-specific, therapeutic approaches, although their clinical applicability still requires further validation. This review discusses the emerging evidence supporting the dual role of iPSC-derived glial EVs in health and disease, underscores the translational potential of iPSC-based platforms for mechanistic studies, and outlines their promise as precision medicine tools for diagnostics and therapy.<\/jats:p>","DOI":"10.3390\/ijms27125182","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:04:14Z","timestamp":1780913054000},"page":"5182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Dual Role of Glial Extracellular Vesicles in Neurodegeneration: Insights from iPSC-Based Models"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7511-035X","authenticated-orcid":false,"given":"Aurora","family":"Scrivo","sequence":"first","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, Bellvitge University Hospital IDIBELL, Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Bernardino","sequence":"additional","affiliation":[{"name":"RISE-Health, UBI, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Consiglio","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, Bellvitge University Hospital IDIBELL, Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Institute of Biomedicine of the University of Barcelona (IBUB), 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114216","DOI":"10.1016\/j.celrep.2024.114216","article-title":"Microglia-astrocyte crosstalk in the amyloid plaque niche of an Alzheimer\u2019s disease mouse model, as revealed by spatial transcriptomics","volume":"43","author":"Mallach","year":"2024","journal-title":"Cell Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1038\/s41467-026-69944-6","article-title":"Multi-modal dissection of cell-type specific TDP-43 pathology in the motor cortex","volume":"17","author":"Ruf","year":"2026","journal-title":"Nat. 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