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Updated: Jun 6, 2025

Derivation of a Human Brain Organoid with Microglia Development
Published on: January 17, 2025
Brain organoid models for studying the function of iPSC-derived microglia in neurodegeneration and brain tumours
Angelica Maria Sabogal-Guaqueta1, Teresa Mitchell-Garcia1, Jasmijn Hunneman1
1Faculty of Science and Engineering, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, The Netherlands.
Abstract:
Microglia represent the main resident immune cells of the brain. The interplay between microglia and other cells in the central nervous system, such as neurons or other glial cells, influences the function and ability of microglia to respond to various stimuli. These cellular communications, when disrupted, can affect the structure and function of the brain, and the initiation and progression of neurodegenerative diseases including Alzheimer's disease and Parkinson's disease, as well as the progression of other brain diseases like glioblastoma. Due to the difficult access to patient brain tissue and the differences reported in the murine models, the available models to study the role of microglia in disease progression are limited. Pluripotent stem cell technology has facilitated the generation of highly complex models, allowing the study of control and patient-derived microglia in vitro. Moreover, the ability to generate brain organoids that can mimic the 3D tissue environment and intercellular interactions in the brain provide powerful tools to study cellular pathways under homeostatic conditions and various disease pathologies. In this review, we summarise the most recent developments in modelling degenerative diseases and glioblastoma, with a focus on brain organoids with integrated microglia. We provide an overview of the most relevant research on intercellular interactions of microglia to evaluate their potential to study brain pathologies.
Insights
Brain organoids with microglia offer advanced models for studying neurodegenerative diseases and glioblastoma. These models improve understanding of microglia
Area of Science:
- Neuroscience
- Immunology
- Stem Cell Biology
Background:
- Microglia are key immune cells in the central nervous system, crucial for brain function.
- Disrupted microglia interactions contribute to neurodegenerative diseases (e.g., Alzheimer's, Parkinson's) and glioblastoma.
- Existing models for studying microglia in disease are limited due to accessibility and species differences.
Purpose of the Study:
- To review recent advancements in modeling neurodegenerative diseases and glioblastoma using brain organoids with integrated microglia.
- To highlight the potential of these advanced models for studying microglia's role in brain pathologies.
Main Methods:
- Utilizing pluripotent stem cell technology to generate complex in vitro models.
- Developing brain organoids that mimic the 3D tissue environment and intercellular interactions.
- Focusing on models incorporating microglia for disease pathology studies.
Main Results:
- Brain organoids with integrated microglia provide a powerful tool for studying cellular pathways.
- These models allow for in vitro investigation of both control and patient-derived microglia.
- Recent developments enable better mimicry of in vivo brain tissue and cell interactions.
Conclusions:
- Brain organoids with integrated microglia represent a significant step forward in disease modeling.
- These models offer enhanced potential for studying intercellular interactions of microglia in brain pathologies.
- Further research using these models can deepen our understanding of neurodegenerative diseases and glioblastoma.

