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

Archives of Pharmacal Research 2020년 43권 9호 p.877 ~ 889
남기홍, 이상아, 장현지, 한정원, 이재철,
소속 상세정보
남기홍 ( Nam Ki-Hong ) - Sungkyunkwan University School of Pharmacy
이상아 ( Yi Sang-Ah ) - Sungkyunkwan University School of Pharmacy
장현지 ( Jang Hyun-Ji ) - Sungkyunkwan University School of Pharmacy
한정원 ( Han Jeung-Whan ) - Sungkyunkwan University School of Pharmacy
이재철 ( Lee Jae-Cheol ) - Sungkyunkwan University School of Pharmacy

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.

키워드

Stem cell; Neurogenesis; Brain organoid; Disease modeling; Neurodevelopmental disease

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