Brain organoid models for studying the function of iPSC-derived microglia in neurodegeneration and brain tumours

Angelica Maria Sabogal-Guaqueta*, Teresa Mitchell-Garcia, Jasmijn Hunneman, Daniëlle Voshart, Arun Thiruvalluvan, Floris Foijer, Frank Kruyt, Marina Trombetta-Lima, Bart J.L. Eggen, Erik Boddeke, Lara Barazzuol, Amalia M. Dolga*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Article number106742
Number of pages16
JournalNeurobiology of Disease
Volume203
DOIs
Publication statusPublished - Dec-2024

Keywords

  • Glioblastoma
  • iPSC
  • Microglia
  • Neurodegenerative diseases
  • Organoids

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