In vitro modeling for inherited neurological diseases using induced pluripotent stem cells: from 2D to organoid
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Online ISSN 1976-3786 Print ISSN 0253-6269
REVIEW
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 Lee1,2,3
Received: 25 June 2020 / Accepted: 29 July 2020 © The Pharmaceutical Society of Korea 2020
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 Ki Hong Nam and Sang Ah Yi are contributed equally. * Jaecheol Lee [email protected] 1
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
2
Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea
3
Imnewrun Biosciences Inc., Suwon 16419, Republic of Korea
the way for accurate modeling of neurological disorders in a dish. Keywords Stem cell · Neurogenesis · Brain organoid · Disease modeling · Neurodevelopmental disease
Introduction Understanding the biological mechanism of neurological disease remains a major issue in neurobiology (Insel and Landis 2013). The human brain consists of various cell types with specific functions and with complex interactions among them. Moreover, diverse genetic, cellular, and environmental factors cause various symptoms and varied severity of neurological diseases (Geschwind and Flint 2015; LlinaresBenadero and Borrell 2019). Despite outstanding developments in neuroscience, neurological disease continues to greatly affect individuals and the society (The Lancet Neurology 2017). Current therapeutics (such as valproic acid for bipolar disorder) were contingently discovered, but did not go through a rational design and development process (López-Muñoz et al. 2018). Our current notion of neuro
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