Brain organoid: a 3D technology for investigating cellular composition and interactions in human neurological development and disease models in vitro

Oluwafemi Solomon Agboola,Yanshuang Wu,Zhiyan Shan,Lei Lei,Xinglin Hu

doi:10.1186/s13287-021-02369-8

Abstract

The study of human brain physiology, including cellular interactions in normal and disease conditions, has been a challenge due to its complexity and unavailability. Induced pluripotent stem cell (iPSC) study is indispensable in the study of the pathophysiology of neurological disorders. Nevertheless, monolayer systems lack the cytoarchitecture necessary for cellular interactions and neurological disease modeling. Brain organoids generated from human pluripotent stem cells supply an ideal environment to model both cellular interactions and pathophysiology of the human brain. This review article discusses the composition and interactions among neural lineage and non-central nervous system cell types in brain organoids, current studies, and future perspectives in brain organoid research. Ultimately, the promise of brain organoids is to unveil previously inaccessible features of neurobiology that emerge from complex cellular interactions and to improve our mechanistic understanding of neural development and diseases.Graphical abstract

Highlights

Organoids are in vitro-derived structures that undergo some level of self-organization and resemble, at least in part, in vivo organs [1]
Different organoid systems can be chosen for specific applications that could be used to generate specific neural structure, the desired cellular composition, and complex cellular interactions (Table 1)
Implantation of brain organoids into the mouse cortex led to an increased population of astrocytes, oligodendrocytes, and microglial cells and prolonged tissue survival contrary to the reports of organoids shrinking in size, probably due to progressive neuronal cell loss [6]

Summary

Introduction

Organoids are in vitro-derived structures that undergo some level of self-organization and resemble, at least in part, in vivo organs [1]. Xiang et al designed a protocol to differentiate human embyonic stem cells (hESCs) to thalamic organoids that can recapitulate thalamus development. Mesodermal progenitors gave rise to microglia-like cells that physically interacted with neurons and were able to phagocytose synaptic structures in brain organoids [25].

Results

Conclusion