Guided and unguided neural organoids play complementary roles in studying neurodevelopment and neuroinflammation

Abstract

OBJECTIVE: This study aimed to compare guided dorsal forebrain neural organoids with unguided neural organoids, focusing on differences in structural organization, cellular composition, and functional properties. METHODS: Using the same human induced pluripotent stem cell line, we applied two established differentiation protocols in parallel to generate guided and unguided neural organoids. RESULTS: Guided neural organoids exhibited reproducible cytoarchitecture, relatively homogeneous morphology, and robust network activity, making them particularly well-suited for modeling specific aspects of cortical neurodevelopment and neurodevelopmental disorders. In contrast, unguided neural organoids displayed greater heterogeneity in morphology and cellular composition, including prominent development of astrocytes, microglia, and choroid plexus-like structures that respond to inflammatory stimuli, positioning them as valuable models for studying neuroinflammation during brain development. CONCLUSION: These findings emphasize the importance of selecting neural organoids protocols based on specific research questions, and suggest that the guided and unguided approaches can complement each other to provide insights into neurodevelopmental and neuroinflammatory processes.