Abstract
Brain organoids have recently emerged as a three-dimensional tissue culture platform to study the principles of neurodevelopment and morphogenesis. Importantly, brain organoids can be derived from human stem cells, and thus offer a model system for early human brain development and human specific disorders. However, there are still major differences between the in vitro systems and in vivo development. This is in part due to the challenge of engineering a suitable culture platform that will support proper development. In this review, we discuss the similarities and differences of human brain organoid systems in comparison to embryonic development. We then describe how organoids are used to model neurodevelopmental diseases. Finally, we describe challenges in organoid systems and how to approach these challenges using complementary bioengineering techniques.
Highlights
Brain organoids are three-dimensional cell cultures that recapitulate key aspects of embryonic brain development [1,2,3,4,5,6] (Figure 1)
Studies revealed additional interspecies differences in the neuronal progenitor population derived from humans, apes, and mice. These include a higher proportion of basal progenitors in human organoids [42], elongation of the times for prometaphase and metaphase of human neuronal progenitors [42], longer proliferative periods of human neuronal progenitors which overlap with the neurogenesis period [44], and slower neuronal maturation dynamics [44,45]
Over the recent years we have witnessed major breakthroughs in stem cell technologies and genome editing, which enabled setting up models to study early human brain development in health and disease
Summary
Brain organoids are three-dimensional cell cultures that recapitulate key aspects of embryonic brain development [1,2,3,4,5,6] (Figure 1). The relative simplicity of brain organoids in comparison to in vivo animals, their accessibility and small size, and the high degree of experimental control turn them into a quantitative biology platform. These features make organoids an exciting system for a wide range of scientific disciplines. (d) Neural differentiation and layer organization induction, ventricle-like lumens appear within the 3D culture. (d) Neural differentiation and layer with neuronal progenitor (PAX6+, red) surrounding the lumen, an intermediate layer of sparse organization with neuronal progenitor (PAX6+, red) surrounding the lumen, an intermediate layer progenitors (DAPI, blue) and neuronal layer (TUJ1+, green) on the organoid periphery. Images of sparse progenitors (DAPI, blue) and neuronal layer (TUJ1+, green) on the organoid periphery. Images adapted from et Karzbrun et al [7]
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