In vitro modeling for inherited neurological diseases using induced pluripotent stem cells: from 2D to organoid

Nam, Ki Hong; Yi, Sang Ah; Jang, Hyun Ji; Han, Jeung-Whan; Lee, Jaecheol

doi:10.1007/s12272-020-01260-z

Review
Published: 05 August 2020

In vitro modeling for inherited neurological diseases using induced pluripotent stem cells: from 2D to organoid

Ki Hong Nam¹,
Sang Ah Yi¹,
Hyun Ji Jang¹,
Jeung-Whan Han¹ &
Jaecheol Lee ORCID: orcid.org/0000-0002-2070-7463^1,2,3

Archives of Pharmacal Research volume 43, pages 877–889 (2020)Cite this article

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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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Ki Hong Nam and Sang Ah Yi are contributed equally.

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School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea
Ki Hong Nam, Sang Ah Yi, Hyun Ji Jang, Jeung-Whan Han & Jaecheol Lee
Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, 16419, Republic of Korea
Jaecheol Lee
Imnewrun Biosciences Inc., Suwon, 16419, Republic of Korea
Jaecheol Lee

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Ki Hong Nam
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Hyun Ji Jang
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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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Received: 25 June 2020
Accepted: 29 July 2020
Published: 05 August 2020
Issue Date: September 2020
DOI: https://doi.org/10.1007/s12272-020-01260-z

Keywords

Stem cell
Neurogenesis
Brain organoid
Disease modeling
Neurodevelopmental disease