{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:21:47Z","timestamp":1790014907250,"version":"4.0.1"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Glial cells play a critical role in neural development, function, and immune regulation, with microglia serving as the principal immune cells of the central nervous system and retina. Although microglia are central to neuroinflammation and disease progression, progress in understanding human microglial biology has been limited by the lack of physiologically relevant\n                    <jats:italic>in vitro<\/jats:italic>\n                    models. Stem cell\u2013derived brain and retinal organoids provide three-dimensional systems that recapitulate human tissue architecture and developmental trajectories, offering new opportunities to study neuroimmune interactions. This review summarizes strategies for integrating microglia into neural organoids through co-differentiation and transplantation, and outlines methodologies for establishing humanized immune microenvironments and assessing microglial maturation, migration, phagocytic function, and inflammatory activation. We highlight applications of organoid\u2013microglia models in neurodevelopmental and neurodegenerative disorders, including autism spectrum disorder, Alzheimer\u2019s disease, and retinal diseases, as well as their potential in drug screening and microglia-targeted interventions. Additionally, emerging technologies\u2014such as organ-on-a-chip platforms, spatial transcriptomics, and multi-omics analyses\u2014are enhancing the physiological relevance and analytical power of these systems. Overall, organoid\u2013microglia platforms bridge a critical gap between conventional cell culture and\n                    <jats:italic>in vivo<\/jats:italic>\n                    models, enabling deeper insights into neuroimmune interactions and accelerating the development of precise immunomodulatory therapies.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1747589","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:50:07Z","timestamp":1773298207000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Organoid\u2013microglia system for modeling the immune microenvironment of the brain and retina"],"prefix":"10.3389","volume":"17","author":[{"given":"Jingjing","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]},{"name":"Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University","place":["Shijiazhuang, Hebei, China"]},{"name":"Hebei International Joint Research Center on Rheumatic Diseases","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binxin","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Biology and Engineering, Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanjing","family":"Gu","sequence":"additional","affiliation":[{"name":"Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]},{"name":"Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University","place":["Shijiazhuang, Hebei, China"]},{"name":"Hebei International Joint Research Center on Rheumatic Diseases","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]},{"name":"Hebei International Joint Research Center on Rheumatic Diseases","place":["Shijiazhuang, Hebei, China"]},{"name":"Hebei Research Center for Stem Cell Medical Translational Engineering","place":["Shijiazhuang, Hebei, 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