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Updated: Aug 18, 2025
Derivation of a Human Brain Organoid with Microglia Development
Published on: January 17, 2025
Microglia-containing human brain organoids for the study of brain development and pathology
Wendiao Zhang1,2,3, Jiamei Jiang1,3, Zhenhong Xu1,3,4
1The First Affiliated Hospital, Multi-Omics Research Center for Brain Disorders, Hengyang Medical School, University of South China, 421001, Hengyang, Hunan, China.
Abstract:
Microglia are resident immune cells in the central nervous system, playing critical roles in brain development and homeostasis. Increasing evidence has implicated microglia dysfunction in the pathogenesis of various brain disorders ranging from psychiatric disorders to neurodegenerative diseases. Using a human cell-based model to illuminate the functional mechanisms of microglia will promote pathological studies and drug development. The recently developed microglia-containing human brain organoids (MC-HBOs), in-vitro three-dimensional cell cultures that recapitulate key features of the human brain, have provided a new avenue to model brain development and pathology. However, MC-HBOs generated from different methods differ in the origin, proportion, and fidelity of microglia within the organoids, and may have produced inconsistent results. To help researchers to develop a robust and reproducible model that recapitulates in-vivo signatures of human microglia to study brain development and pathology, this review summarized the current methods used to generate MC-HBOs and provided opinions on the use of MC-HBOs for disease modeling and functional studies.
Insights
Microglia dysfunction is linked to brain disorders. This review examines microglia-containing human brain organoids (MC-HBOs) to improve modeling of brain development and disease.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia are crucial for brain health and homeostasis.
- Microglia dysfunction contributes to various neurological and psychiatric disorders.
- Human brain organoids offer a model for studying brain development and pathology.
Purpose of the Study:
- To review methods for generating microglia-containing human brain organoids (MC-HBOs).
- To discuss the use of MC-HBOs for modeling brain development and disease.
- To guide researchers in developing robust and reproducible MC-HBO models.
Main Methods:
- Review of current literature on MC-HBO generation techniques.
- Analysis of microglia origin, proportion, and fidelity in different MC-HBO models.
- Comparative assessment of MC-HBOs for disease modeling and functional studies.
Main Results:
- Existing MC-HBO generation methods vary, impacting microglia characteristics.
- Inconsistent microglia representation can lead to unreliable research outcomes.
- Standardization is needed for reproducible MC-HBO models.
Conclusions:
- MC-HBOs are a promising tool for studying human microglia in health and disease.
- Further refinement of MC-HBO generation is necessary for consistent and valid results.
- Standardized MC-HBO models will advance brain disorder research and therapeutic development.
