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Human Neural Organoids for Studying Brain Cancer and Neurodegenerative Diseases
Published on: June 28, 2019
Human iPSC-derived microglial cells protect neurons from neurodegeneration in long-term cultured adhesion brain
Xianwei Chen1,2, Guoqiang Sun1, Lizhao Feng1
1Department of Neurodegenerative Diseases, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, CA, 91010, USA.
Abstract:
Brain organoid models have greatly facilitated our understanding of human brain development and disease. However, key brain cell types, such as microglia, are lacking in most brain organoid models. Because microglia have been shown to play important roles in brain development and pathologies, attempts have been made to add microglia to brain organoids through co-culture. However, only short-term microglia-organoid co-cultures can be established, and it remains challenging to have long-lasting survival of microglia in organoids to mimic long-term residency of microglia in the brain. In this study, we developed an adhesion brain organoid (ABO) platform that allows prolonged culture of brain organoids (greater than a year). Moreover, the long-term (LT)-ABO system contains abundant astrocytes and can support prolonged survival and ramification of microglia. Furthermore, we showed that microglia in the LT-ABO could protect neurons from neurodegeneration by increasing synaptic density and reducing p-Tau level and cell death in the LT-ABO. Therefore, the microglia-containing LT-ABO platform generated in this study provides a promising human cellular model for studying neuron-glia and glia-glia interactions in brain development and the pathogenesis of neurodegenerative diseases such as Alzheimer's disease.
Insights
This study introduces a novel long-term adhesion brain organoid (LT-ABO) platform that successfully incorporates microglia. This advanced model supports prolonged microglia survival, offering new possibilities for studying neurodegenerative diseases like Alzheimer's disease.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Brain organoids are crucial for studying brain development and disease.
- Most organoids lack microglia, essential for brain function and pathology.
- Current microglia-organoid co-cultures are short-term, limiting research on long-term interactions.
Purpose of the Study:
- To develop a brain organoid model with long-term microglia survival.
- To investigate the role of microglia in neuroprotection within organoids.
- To create a platform for studying neurodegenerative diseases and neuron-glia interactions.
Main Methods:
- Development of an adhesion brain organoid (ABO) platform for prolonged culture (>1 year).
- Incorporation of microglia into the ABO system, creating a long-term ABO (LT-ABO).
- Assessment of microglia survival, ramification, and neuroprotective effects in the LT-ABO.
Main Results:
- The LT-ABO platform supports prolonged survival and ramification of microglia.
- Microglia in the LT-ABO demonstrated neuroprotective effects.
- These effects included increased synaptic density and reduced p-Tau levels and cell death.
Conclusions:
- The LT-ABO system provides a robust model for long-term microglia-brain organoid interactions.
- This platform facilitates the study of neuron-glia and glia-glia interactions in brain development.
- The LT-ABO is a promising model for investigating neurodegenerative diseases, including Alzheimer's disease.
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