中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (12): 3448-3460.doi: 10.4103/NRR.NRR-D-24-00921

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

含小胶质细胞的脑类器官的生成、研究和未来应用

  

  • 出版日期:2025-12-15 发布日期:2025-03-13

Generation, interrogation, and future applications of microglia-containing brain organoids

Julia Di Stefano1, 2, *, Federica Di Marco3, 4, Ilaria Cicalini3, 4, Una FitzGerald5, 6, Damiana Pieragostino3, 4, Marleen Verhoye2, 7, Peter Ponsaerts1, #, Elise Van Breedam1, #   

  1. 1 Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Wilrijk, Belgium;  2 Bio-Imaging Lab, University of Antwerp, Wilrijk, Belgium;  3 Center for Advanced Studies and Technology (CAST), G. d’Annunzio University of Chieti-Pescara, Chieti, Italy;  4 Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy;  5 CÚRAM, Center for Research in Medical Devices, Biomedical Engineering, University of Galway, Ireland;  6 Galway Neuroscience Center, University of Galway, Ireland;  7μNEURO Research Center of Excellence, University of Antwerp, Wilrijk, Belgium
  • Online:2025-12-15 Published:2025-03-13
  • Contact: Julia Di Stefano, PhD, julia.distefano@uantwerpen.be.
  • Supported by:
    This work and the PhD fellowship of JDS were funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 813263 (PMSMatTrain, granted to UF, PP, MV, and DP). Additional support was provided by the Fund for Scientific Research Flanders (FWO-Vlaanderen) of the Flemish Government (FWO sabbatical bench fee K800224N granted to PP) and ERA-NET RePark (granted to PP).

摘要: https://orcid.org/0000-0003-3825-9803 (Julia Di Stefano)

Abstract: Brain organoids encompass a large collection of in vitro stem cell–derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function. First, this review provides a brief introduction to the current state-of-the-art for neuroectoderm brain organoid development, emphasizing their biggest advantages in comparison with classical two-dimensional cell cultures and animal models. However, despite their usefulness for developmental studies, a major limitation for most brain organoid models is the absence of contributing cell types from endodermal and mesodermal origin. As such, current research is highly investing towards the incorporation of a functional vasculature and the microglial immune component. In this review, we will specifically focus on the development of immune-competent brain organoids. By summarizing the different approaches applied to incorporate microglia, it is highlighted that immune-competent brain organoids are not only important for studying neuronal network formation, but also offer a clear future as a new tool to study inflammatory responses in vitro in 3D in a brainlike environment. Therefore, our main focus here is to provide a comprehensive overview of assays to measure microglial phenotype and function within brain organoids, with an outlook on how these findings could better understand neuronal network development or restoration, as well as the influence of physical stress on microglia-containing brain organoids. Finally, we would like to stress that even though the development of immunecompetent brain organoids has largely evolved over the past decade, their full potential as a pre-clinical tool to study novel therapeutic approaches to halt or reduce inflammationmediated neurodegeneration still needs to be explored and validated. 

Key words: 3D cell culture, brain organoids, immune response, immunocompetent model, in vitro model, microglia, neural organoids, neuroimmunology, neuroinflammation