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Review
, 42 (9), 617-627

Past, Present, and Future of Brain Organoid Technology

Affiliations
Review

Past, Present, and Future of Brain Organoid Technology

Bonsang Koo et al. Mol Cells.

Abstract

Brain organoids are an exciting new technology with the potential to significantly change our understanding of the development and disorders of the human brain. With step-by-step differentiation protocols, three-dimensional neural tissues are self-organized from pluripotent stem cells, and recapitulate the major millstones of human brain development in vitro. Recent studies have shown that brain organoids can mimic the spatiotemporal dynamicity of neurogenesis, the formation of regional neural circuitry, and the integration of glial cells into a neural network. This suggests that brain organoids could serve as a representative model system to study the human brain. In this review, we will overview the development of brain organoid technology, its current progress and applications, and future prospects of this technology.

Keywords: brain disorder; brain organoid; neurodevelopment; pluripotent stem cell; three-dimensional culture.

Conflict of interest statement

Disclosure

The authors have no potential conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1. History of brain organoid research
Organoid technology started from the research on re-aggregation of sponge cells, suggesting self-organization plays a key role in organ formation (Tung and Kü, 1944; Wilson, 1907; Zwilling, 1960). PSCs including embryonic stem cells and induced pluripotent cells were established (Martin, 1981; Takahashi and Yamanaka, 2006; Thomson et al., 1998). With these stem cell lines, various types of organoids are developed from intestine to hippocampus (Lancaster et al., 2013; Sakaguchi et al., 2015; Sato et al., 2009; Xia et al., 2014; Zhong et al., 2014). Brain organoid models have been widely used to study human brain disorders, including ZIKV infection. Bioengineering technologies are being developed to address the current limitations of organoids such as oxygen deprivation during long-term culture (Grebenyuk and Ranga, 2019).
Fig. 2
Fig. 2. Brief protocols of brain specific organoids generation
On the top, frequently used chemical reagents are summarized. On the bottom, brief schematics of organoid generation are described in time order, with critical components of culture media.
Fig. 3
Fig. 3. Advances in brain organoid technology
Multidisciplinary bioengineering techniques provide a breakthrough to overcome the limitations of the current brain organoid technology. Tissue engineering approaches, such as 3D bioprinting, enable the rationally-designed organization of various type of cells in brain organoids. The region-specific brain organoids can be fused together to induce the integration of neural networks between distinct regions. Non-neuronal cells can be incorporated into brain organoids to model the interactions among neurons, glia, immune cells, and vasculature (left panel). The brain organoid technology has great translational potential for modeling brain disorders and screening therapeutic drugs. Brain organoids from patient-derived iPSCs are relevant platforms for studying brain cancer, neurodevelopmental and neurodegenerative disorders. Patient-specific mutations or oncogenes can be introduced into brain organoids using CRISPR/Cas9 technology to investigate the genetic mechanisms of brain disorders. In addition, a personalized drug screening using patient-derived organoids could predict drug efficacy before a drug treatment of patients (right panel).

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