ArticleStem cell reviews and reports2026
Generating Microglia-Integrated Cortical Organoids from Human Embryonic Stem Cells.
Article in Stem cell reviews and reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
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Abstract
Brain organoids require the integration of microglia to faithfully recapitulate physiological brain functions, as these immune cells are critical for neurodevelopmental processes and homeostatic regulation. Here, we present a protocol for generating cortical organoids integrated with microglial progenitors derived from human embryonic stem cells (hESCs) by differentiating hESCs into Yolk Sac Embryoid Bodies (YS-EBs). Within the cultured organoids, the integrated microglia progenitors undergo differentiation, migration, and maturation. Key optimizations include enhanced microglial progenitor yield and organoid maturation, optimized integration timing, and implementation of standardized cryosectioning and dual tissue-clearing methods (iDISCO, CUBIC) to enable comprehensive 2D and 3D validation of microglial integration and their interactions with neural cells. This protocol supports long-term co-culture (up to 46 days) with minimal necrotic core formation, enabling studies of neuroimmune interactions in a physiologically relevant 3D human brain model.
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