Organoid technology for brain and therapeutics research.

Brain is one of the most complex organs in human. The current brain research is mainly based on the animal models and traditional cell culture. However, the inherent species differences between humans and animals as well as the gap between organ level and cell level make it difficult to study human brain development and associated disorders through traditional technologies. Recently, the brain organoids derived from pluripotent stem cells have been reported to recapitulate many key features of human brain in vivo, for example recapitulating the zone of putative outer radial glia cells. Brain organoids offer a new platform for scientists to study brain development, neurological diseases, drug discovery and personalized medicine, regenerative medicine, and so on. Here, we discuss the progress, applications, advantages, limitations, and prospects of brain organoid technology in neurosciences and related therapeutics.

Wang Z ，Wang SN ，Xu TY ，Miao ZW ，Su DF ，Miao CY ... -  《-》

Three-dimensional in vitro tissue culture models of brain organoids.

Brain organoids are three-dimensional self-assembled structures that are derived from human induced pluripotent stem cells (hiPSCs). They can recapitulate the spatiotemporal organization and function of the brain, presenting a robust system for in vitro modeling of brain development, evolution, and diseases. Significant advances in biomaterials, microscale technologies, gene editing technologies, and stem cell biology have enabled the construction of human specific brain structures in vitro. However, the limitations of long-term culture, necrosis, and hypoxic cores in different culture models obstruct brain organoid growth and survival. The in vitro models should facilitate oxygen and nutrient absorption, which is essential to generate complex organoids and provides a biomimetic microenvironment for modeling human brain organogenesis and human diseases. This review aims to highlight the progress in the culture devices of brain organoids, including dish, bioreactor, and organ-on-a-chip models. With the modulation of bioactive molecules and biomaterials, the generated organoids recapitulate the key features of the human brain in a more reproducible and hyperoxic fashion. Furthermore, an outlook for future preclinical studies and the genetic modifications of brain organoids is presented.

Gong J ，Meng T ，Yang J ，Hu N ，Zhao H ，Tian T ... -  《-》

Building brains in a dish: Prospects for growing cerebral organoids from stem cells.

The recent development of organoid techniques, in which embryonic brain-like tissue can be grown from human or mouse stem cells in vitro offers the potential to transform the way in which brain development is studied. In this review, we summarize key aspects of the embryonic development of mammalian forebrains, focussing in particular on the cerebral cortex and highlight significant differences between mouse and primates, including human. We discuss recent work using cerebral organoids that has revealed key similarities and differences between their development and that of the brain in vivo. Finally, we outline the ways in which cerebral organoids can be used in combination with CRISPR/Cas9 genome editing to unravel genetic mechanisms that control embryonic development of the cerebral cortex, how this can help us understand the causes of neurodevelopmental disorders and some of the key challenges which will have to be resolved before organoids can become a mainstream tool to study brain development.

Mason JO ，Price DJ 《-》

Organoid technology for tissue engineering.

For centuries, attempts have been continuously made to artificially reconstitute counterparts of in vivo organs from their tissues or cells. Only in the recent decade has organoid technology as a whole technological field systematically emerged and been shown to play important roles in tissue engineering. Based on their self-organizing capacities, stem cells of versatile organs, both harvested and induced, can form 3D structures that are structurally and functionally similar to their in vivo counterparts. These organoid models provide a powerful platform for elucidating the development mechanisms, modeling diseases, and screening drug candidates. In this review, we will summarize the advances of this technology for generating various organoids of tissues from the three germ layers and discuss their drawbacks and prospects for tissue engineering.

He J ，Zhang X ，Xia X ，Han M ，Li F ，Li C ，Li Y ，Gao D ... -  《-》

Past, Present, and Future of Brain Organoid Technology.

Koo B ，Choi B ，Park H ，Yoon KJ ... -  《-》