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Modeling of Hypoxic Brain Injury through 3D Human Neural Organoids

Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 1 Gwanakro, Gwanak-gu, Seoul 08826, Korea
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Academic Editor: Evelyne Gozal
Cells 2021, 10(2), 234; https://doi.org/10.3390/cells10020234
Received: 18 December 2020 / Revised: 14 January 2021 / Accepted: 22 January 2021 / Published: 25 January 2021
(This article belongs to the Special Issue Reprogrammed Cells in Disease Modeling and Drug Discovery)
Brain organoids have emerged as a novel model system for neural development, neurodegenerative diseases, and human-based drug screening. However, the heterogeneous nature and immature neuronal development of brain organoids generated from pluripotent stem cells pose challenges. Moreover, there are no previous reports of a three-dimensional (3D) hypoxic brain injury model generated from neural stem cells. Here, we generated self-organized 3D human neural organoids from adult dermal fibroblast-derived neural stem cells. Radial glial cells in these human neural organoids exhibited characteristics of the human cerebral cortex trend, including an inner (ventricular zone) and an outer layer (early and late cortical plate zones). These data suggest that neural organoids reflect the distinctive radial organization of the human cerebral cortex and allow for the study of neuronal proliferation and maturation. To utilize this 3D model, we subjected our neural organoids to hypoxic injury. We investigated neuronal damage and regeneration after hypoxic injury and reoxygenation. Interestingly, after hypoxic injury, reoxygenation restored neuronal cell proliferation but not neuronal maturation. This study suggests that human neural organoids generated from neural stem cells provide new opportunities for the development of drug screening platforms and personalized modeling of neurodegenerative diseases, including hypoxic brain injury. View Full-Text
Keywords: human brain organoid; cerebral cortex; brain ischemia model; neural stem cell; reoxygenation human brain organoid; cerebral cortex; brain ischemia model; neural stem cell; reoxygenation
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MDPI and ACS Style

Kim, M.S.; Kim, D.-H.; Kang, H.K.; Kook, M.G.; Choi, S.W.; Kang, K.-S. Modeling of Hypoxic Brain Injury through 3D Human Neural Organoids. Cells 2021, 10, 234. https://doi.org/10.3390/cells10020234

AMA Style

Kim MS, Kim D-H, Kang HK, Kook MG, Choi SW, Kang K-S. Modeling of Hypoxic Brain Injury through 3D Human Neural Organoids. Cells. 2021; 10(2):234. https://doi.org/10.3390/cells10020234

Chicago/Turabian Style

Kim, Min S., Da-Hyun Kim, Hyun K. Kang, Myung G. Kook, Soon W. Choi, and Kyung-Sun Kang. 2021. "Modeling of Hypoxic Brain Injury through 3D Human Neural Organoids" Cells 10, no. 2: 234. https://doi.org/10.3390/cells10020234

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