Trends and challenges in modeling glioma using 3D human brain organoids

Abstract

The human brain organoids derived from pluripotent cells are a new class of three-dimensional tissue systems that recapitulates several neural epithelial aspects. Brain organoids have already helped efficient modeling of crucial elements of brain development and disorders. Brain organoids' suitability in modeling glioma has started to emerge, offering another usefulness of brain organoids in disease modeling. Although the current state-of-the organoids mostly reflect the immature state of the brain, with their vast cell diversity, human brain-like cytoarchitecture, feasibility in culturing, handling, imaging, and tractability can offer enormous potential in reflecting the glioma invasion, integration, and interaction with different neuronal cell types. Here, we summarize the current trend of employing brain organoids in glioma modeling and discuss the immediate challenges. Solving them might lay a foundation for using brain organoids as a pre-clinical 3D substrate to dissect the glioma invasion mechanisms in detail.

Fig. 1. Examples of iPSCs-derived human brain organoids.

A Brain organoids shown here exhibits morphologically similar appearances of human neural epithelial tissues with fluid-filled regions. The images adopted from Gabriel et al. EMBO Journal 2016. B Schematic illustrations of various glioma invasion assays that used patient derived GSCs and human brain organoids. Schemes also explain different methods of optimization and what they can reveal.