Brain Organoids: Studying Human Brain Development and Diseases in a Dish.

Jie Xu,Zhexing Wen,Xuekun Li

doi:10.1155/2021/5902824

Abstract

With the rapid development of stem cell technology, the advent of three-dimensional (3D) cultured brain organoids has opened a new avenue for studying human neurodevelopment and neurological disorders. Brain organoids are stem-cell-derived 3D suspension cultures that self-assemble into an organized structure with cell types and cytoarchitectures recapitulating the developing brain. In recent years, brain organoids have been utilized in various aspects, ranging from basic biology studies, to disease modeling, and high-throughput screening of pharmaceutical compounds. In this review, we overview the establishment and development of brain organoid technology, its recent progress, and translational applications, as well as existing limitations and future directions.

Highlights

Being the control center of the nervous system in humans, the brain is one of the most complex and advanced organs in the body, and it has never been easy to study the biological basis of brain development and brain disorders
Recent clinical data reported leakage of blood proteins into cerebrospinal fluid (CSF) in more than 40% of patients tested [97], which was in support of this finding as the disruption of choroid plexus (ChP) integrity would be expected to lead to leakage in the blood-CSF barrier (B-CSF-B)
We summarized many recent advanced techniques in the field of brain organoids, such as the development of assembloids, incorporation of cellular and structural components, and other optimized culture systems

Summary

Introduction

Being the control center of the nervous system in humans, the brain is one of the most complex and advanced organs in the body, and it has never been easy to study the biological basis of brain development and brain disorders. While monolayer (two-dimensional) cell culture has provided a system that can efficiently produce relatively homogeneous population of a cell type, they still cannot recapitulate many characteristic features of the human brain, such as self-organizing properties and interactive dynamics [9, 10] These limitations inspired the innovation of a more sophisticated model system and led to the invention of brain organoids. A comprehensive assessment on the maturation of human cortical organoids reported attainment of early postnatal features when cultured for 250~300 days in vitro, which was in a timeline paralleling in vivo development These features included switches in the histone deacetylase complex and NMDA receptor isoform, as well as the emergence of superficial layer neurons and astrocytes at later stages [21]. We discuss the limitations of organoid models and highlight potential improvements that would allow brain organoids to progress further in the future

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Methods of generation outcomes

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Conclusions and Discussion