2025/07/23 by Xabier Cuesta‐Puente, Marco González-Domínguez, Marta Pereira‐Iglesias +6 · 1 voice
Neuroscience · Immunology and Microbiology · #Neuroinflammation and Neurodegeneration Mechanisms #Immune cells in cancer #Neurogenesis and neuroplasticity mechanisms
paper · pdf · doi:10.1002/glia.70062
openalex publication_date 2025/07/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Cerebral organoids derived from human induced pluripotent stem cells (iPSCs) are increasingly becoming essential tools to study the human brain, from understanding pathological mechanisms in neurodevelopmental, neurodegenerative, and infectious diseases to identifying genetic risks and biomarkers. To resemble the brain environment, cerebral organoids must contain microglia, the resident macrophages of the brain parenchyma that are essential for its homeostasis. As microglia derive from the yolk sac, they are not present in conventional brain organoids, which are generated by reprogramming iPSCs towards the neuroectodermal lineage and must be exogenously incorporated through a variety of strategies. Once in the organoid parenchyma, microglia must recapitulate their developmental milestones to achieve full immunocompetence, reaching a mature transcriptional profile and morphology, a tessellated distribution, efficient phagocytosis, and controlled inflammatory responses. In this review, we will summarize recent protocols that have been developed to generate human microglial-containing cerebral organoids (MCCOs), focusing on the methods used to assess the level of microglial maturation compared to their in vivo counterparts. We provide a series of recommendations to assess microglial immunocompetence using stringent quantitative approaches that will promote developing standardized protocols to culture MCCOs.