Abstract
Stem cells are characterized by self-renewal and by their ability to differentiate into cells of various organs. With massive progress in 2D and 3D cell culture techniques, in vitro generation of various types of such organoids from patient-derived stem cells is now possible. As in vitro differentiation protocols are usually made to resemble human developmental processes, organogenesis of patient-derived stem cells can provide key information regarding a range of developmental diseases. Human stem cell-based in vitro modeling as opposed to using animal models can particularly benefit the evaluation of neurological diseases because of significant differences in structure and developmental processes between the human and the animal brain. This review focuses on stem cell-based in vitro modeling of neurodevelopmental disorders, more specifically, the fundamentals and technical advancements in monolayer neuron and brain organoid cultures. Furthermore, we discuss the drawbacks of the conventional culture method and explore the advanced, cutting edge 3D organoid models for several neurodevelopmental diseases, including genetic diseases such as Down syndrome, Rett syndrome, and Miller–Dieker syndrome, as well as brain malformations like macrocephaly and microcephaly. Finally, we discuss the limitations of the current organoid techniques and some potential solutions that pave the way for accurate modeling of neurological disorders in a dish.
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Acknowledgements
This research was financially supported through grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2017R1A6A3A04001986, 2019R1C1C1010675, 2019R1I1A1A01058903, and 2019R1A5A2027340).
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Jaecheol Lee is employee of Imnewrun Biosciences Inc. The remaining authors declares no competing interest.
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Nam, K.H., Yi, S.A., Jang, H.J. et al. In vitro modeling for inherited neurological diseases using induced pluripotent stem cells: from 2D to organoid. Arch. Pharm. Res. 43, 877–889 (2020). https://doi.org/10.1007/s12272-020-01260-z
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DOI: https://doi.org/10.1007/s12272-020-01260-z