Abstract
Simple SummaryThis review article describes an overview of the developed advanced neural in vitro systems and the discovery of brain organoids including the recently developed improvement of this innovative technology. We also mention the main disease modeling applications of brain organoids and their potential impact in biomedical applications.Neurological disorders are among the leading causes of death worldwide, accounting for almost all onsets of dementia in the elderly, and are known to negatively affect motor ability, mental and cognitive performance, as well as overall wellbeing and happiness. Currently, most neurological disorders go untreated due to a lack of viable treatment options. The reason for this lack of options is s poor understanding of the disorders, primarily due to research models that do not translate well into the human in vivo system. Current models for researching neurological disorders, neurodevelopment, and drug interactions in the central nervous system include in vitro monolayer cell cultures, and in vivo animal models. These models have shortcomings when it comes to translating research about disorder pathology, development, and treatment to humans. Brain organoids are three-dimensional (3D) cultures of stem cell-derived neural cells that mimic the development of the in vivo human brain with high degrees of accuracy. Researchers have started developing these miniature brains to model neurodevelopment, and neuropathology. Brain organoids have been used to model a wide range of neurological disorders, including the complex and poorly understood neurodevelopmental and neurodegenerative disorders. In this review, we discuss the brain organoid technology, placing special focus on the different brain organoid models that have been developed, discussing their strengths, weaknesses, and uses in neurological disease modeling.
Highlights
Neurological disorders are a group of disorders affecting the central and peripheral nervous systems
According to the WHO, hundreds of millions of people worldwide are affected by neurological disorders, counting more than 6 million people who die because of stroke every year, over 50 million people who suffer from epilepsy, and almost 50 million people who have dementia, among which 60–70% is thought to be a direct consequence of Alzheimer’s disease (AD)
The ectoderm includes most of the cells that we commonly find in the central nervous system (CNS), including cells of the brain such as neurons, astrocytes and oligodendrocytes, and the peripheral nervous system (PNS), and epithelial cell lines [19]
Summary
Neurological disorders are a group of disorders affecting the central and peripheral nervous systems. Employed as a monolayer cell (co-)culture, this model gives researchers the ability to study the impact of potentially pathogenic mutations when working with human cells as opposed to animal cells Shortcomings of this kind of model include the lack of cellular diversity and interconnectivity (especially in the highly regulated and interconnective 3D environment of the brain) in a 2D monolayer culture, as well as lacking proper presentation of disease pathology, development, and symptoms. A recent estimate has shown that more than 1000 pathological genetic mutations are commonly shared between a range of neurodegenerative and neurodevelopmental disorders [3,4] This overlap provides researchers the understanding that most neurological disorders do not have a single (or even a few) fate-determining mutations, but rather a large and complex set of interactions between malfunctioning genes, the aging process, and in vivo-, and environmental factors [3,4]. By using the patient’s own cells, iPSCs can be generated and used for transplantation therapy, as the genetic code and immunogenic profile will match the immune system of the host of the grafted cells [16,17,18]
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