Microglia-containing human brain organoids for the study of brain development and pathology

Zhang, Wendiao; Jiang, Jiamei; Xu, Zhenhong; Yan, Hongye; Tang, Beisha; Liu, Chun Yu; Chen, Chao; Meng, Qingtuan

doi:10.1038/s41380-022-01892-1

Cited by 46 publications

(33 citation statements)

References 119 publications

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“…Previous studies have integrated microglia into 3D neuronal cultures using various strategies 29 , and in contrast to 2D and mouse models, microglia cultured in 3D remain in a more stable homeostatic state 30 . However, achieving long term organoid-microglia co-cultures at scale has been a challenge for the field.…”

Section: Discussionmentioning

confidence: 99%

Neuroimmune cortical organoids overexpressing C4A exhibit multiple schizophrenia endophenotypes

Stanton¹,

Modan²,

Taylor³

et al. 2023

Preprint

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Elevated expression of the complement component 4A (C4A) protein has been linked to an increased risk of schizophrenia (SCZ). However, there are few human models available to study the mechanisms by which C4A contributes to the development of SCZ. In this study, we established a C4A overexpressing neuroimmune cortical organoid (NICO) model, which includes mature neuronal cells, astrocytes, and functional microglia. The C4A NICO model recapitulated several neuroimmune endophenotypes observed in SCZ patients, including modulation of inflammatory genes and increased cytokine secretion. C4A expression also increased microglia-mediated synaptic uptake in the NICO model, supporting the hypothesis that synapse and brain volume loss in SCZ patients may be due to excessive microglial pruning. Our results highlight the role of C4A in the immunogenetic risk factors for SCZ and provide a human model for phenotypic discovery and validation of immunomodulating therapies.

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Section: Discussionmentioning

confidence: 99%

Neuroimmune cortical organoids overexpressing C4A exhibit multiple schizophrenia endophenotypes

Stanton¹,

Modan²,

Taylor³

et al. 2023

Preprint

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“…As astrocytes are permissive to SARS‐CoV‐2, brain organoids co‐culturing with astrocytes might boost the viral infection rate 82 . Microglia, the resident immune cells of the central nervous system, play vital roles in brain development, homeostasis, and diseases, incorporating microglia into neural organoids provides unprecedented opportunities to study infective neurological disorders 165–169 . For instance, upon ZIKV infection, microglia became activated and targeted neurons and excessively pruned synapses in microglia‐containing brain organoids 168 .…”

Section: Challenges and Future Considerationsmentioning

confidence: 99%

Development trends of human organoid‐based COVID‐19 research based on bibliometric analysis

Yuan

Zou

et al. 2023

Cell Proliferation

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Coronavirus disease 2019 (COVID‐19), a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has posed a catastrophic threat to human health worldwide. Human stem cell‐derived organoids serve as a promising platform for exploring SARS‐CoV‐2 infection. Several review articles have summarized the application of human organoids in COVID‐19, but the research status and development trend of this field have seldom been systematically and comprehensively studied. In this review, we use bibliometric analysis method to identify the characteristics of organoid‐based COVID‐19 research. First, an annual trend of publications and citations, the most contributing countries or regions and organizations, co‐citation analysis of references and sources and research hotspots are determined. Next, systematical summaries of organoid applications in investigating the pathology of SARS‐CoV‐2 infection, vaccine development and drug discovery, are provided. Lastly, the current challenges and future considerations of this field are discussed. The present study will provide an objective angle to identify the current trend and give novel insights for directing the future development of human organoid applications in SARS‐CoV‐2 infection.

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“…Adjustment of protocols has been tried by the implementation of endothelial cells in the developing organoids to result in an elementary circulatory system [ 121 ]. IPSC-derived microglia have also been added to organoids to create a self-renewing microglia population [ 122 ].…”

Section: Potential and Limitations Of Brain Organoids For Migrainementioning

confidence: 99%

Human Brain Organoids in Migraine Research: Pathogenesis and Drug Development

Gazerani

2023

IJMS

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Human organoids are small, self-organized, three-dimensional (3D) tissue cultures that have started to revolutionize medical science in terms of understanding disease, testing pharmacologically active compounds, and offering novel ways to treat disease. Organoids of the liver, kidney, intestine, lung, and brain have been developed in recent years. Human brain organoids are used for understanding pathogenesis and investigating therapeutic options for neurodevelopmental, neuropsychiatric, neurodegenerative, and neurological disorders. Theoretically, several brain disorders can be modeled with the aid of human brain organoids, and hence the potential exists for understanding migraine pathogenesis and its treatment with the aid of brain organoids. Migraine is considered a brain disorder with neurological and non-neurological abnormalities and symptoms. Both genetic and environmental factors play essential roles in migraine pathogenesis and its clinical manifestations. Several types of migraines are classified, for example, migraines with and without aura, and human brain organoids can be developed from patients with these types of migraines to study genetic factors (e.g., channelopathy in calcium channels) and environmental stressors (e.g., chemical and mechanical). In these models, drug candidates for therapeutic purposes can also be tested. Here, the potential and limitations of human brain organoids for studying migraine pathogenesis and its treatment are communicated to generate motivation and stimulate curiosity for further research. This must, however, be considered alongside the complexity of the concept of brain organoids and the neuroethical aspects of the topic. Interested researchers are invited to join the network for protocol development and testing the hypothesis presented here.

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Microglia-containing human brain organoids for the study of brain development and pathology

Cited by 46 publications

References 119 publications

Neuroimmune cortical organoids overexpressing C4A exhibit multiple schizophrenia endophenotypes

Neuroimmune cortical organoids overexpressing C4A exhibit multiple schizophrenia endophenotypes

Development trends of human organoid‐based COVID‐19 research based on bibliometric analysis

Human Brain Organoids in Migraine Research: Pathogenesis and Drug Development

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