Production of Highly Uniform Midbrain Organoids from Human Pluripotent Stem Cells

Brain organoids have been considered as an advanced platform for in vitro disease modeling and drug screening, but numerous roadblocks exist, such as lack of large-scale production technology and lengthy protocols with multiple manipulation steps, impeding the industrial translation of brain organoi...

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Main Authors: Xuerui Yao, Ji Hyun Kang, Kee-Pyo Kim, Hyogeun Shin, Zhe-Long Jin, Hao Guo, Yong-Nan Xu, Ying-Hua Li, Sai Hali, Jeongwoo Kwon, Hyeonwoo La, Chanhyeok Park, Yong-June Kim, Lin Wang, Kwonho Hong, Qilong Cao, Il-Joo Cho, Nam-Hyung Kim, Dong Wook Han
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2023/3320211
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author Xuerui Yao
Ji Hyun Kang
Kee-Pyo Kim
Hyogeun Shin
Zhe-Long Jin
Hao Guo
Yong-Nan Xu
Ying-Hua Li
Sai Hali
Jeongwoo Kwon
Hyeonwoo La
Chanhyeok Park
Yong-June Kim
Lin Wang
Kwonho Hong
Qilong Cao
Il-Joo Cho
Nam-Hyung Kim
Dong Wook Han
author_facet Xuerui Yao
Ji Hyun Kang
Kee-Pyo Kim
Hyogeun Shin
Zhe-Long Jin
Hao Guo
Yong-Nan Xu
Ying-Hua Li
Sai Hali
Jeongwoo Kwon
Hyeonwoo La
Chanhyeok Park
Yong-June Kim
Lin Wang
Kwonho Hong
Qilong Cao
Il-Joo Cho
Nam-Hyung Kim
Dong Wook Han
author_sort Xuerui Yao
collection DOAJ
description Brain organoids have been considered as an advanced platform for in vitro disease modeling and drug screening, but numerous roadblocks exist, such as lack of large-scale production technology and lengthy protocols with multiple manipulation steps, impeding the industrial translation of brain organoid technology. Here, we describe the high-speed and large-scale production of midbrain organoids using a high-throughput screening-compatible platform within 30 days. Micro midbrain organoids (µMOs) exhibit a highly uniform morphology and gene expression pattern with minimal variability. Notably, µMOs show dramatically accelerated maturation, resulting in the generation of functional µMOs within only 30 days of differentiation. Furthermore, individual µMOs display highly consistent responsiveness to neurotoxin, suggesting their usefulness as an in vitro high-throughput drug toxicity screening platform. Collectively, our data indicate that µMO technology could represent an advanced and robust platform for in vitro disease modeling and drug screening for human neuronal diseases.
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publisher Wiley
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spelling doaj-art-a429f20de04345d09ff67eca862e03f62025-08-20T02:20:21ZengWileyStem Cells International1687-96782023-01-01202310.1155/2023/3320211Production of Highly Uniform Midbrain Organoids from Human Pluripotent Stem CellsXuerui Yao0Ji Hyun Kang1Kee-Pyo Kim2Hyogeun Shin3Zhe-Long Jin4Hao Guo5Yong-Nan Xu6Ying-Hua Li7Sai Hali8Jeongwoo Kwon9Hyeonwoo La10Chanhyeok Park11Yong-June Kim12Lin Wang13Kwonho Hong14Qilong Cao15Il-Joo Cho16Nam-Hyung Kim17Dong Wook Han18Guangdong Provincial Key Laboratory of Large Animal Models for BiomedicineLaboratory of Stem Cells and OrganoidsDepartment of Life SciencesCenter for BioMicrosystemsGuangdong Provincial Key Laboratory of Large Animal Models for BiomedicineGuangdong Provincial Key Laboratory of Large Animal Models for BiomedicineGuangdong Provincial Key Laboratory of Large Animal Models for BiomedicineGuangdong Provincial Key Laboratory of Large Animal Models for BiomedicineInstitute of OphthalmologyPrimate Resources CenterDepartment of Stem Cell and Regenerative BiotechnologyDepartment of Stem Cell and Regenerative BiotechnologyDepartment of UrologyResearch and Development DepartmentDepartment of Stem Cell and Regenerative BiotechnologyResearch and Development DepartmentCenter for BioMicrosystemsGuangdong Provincial Key Laboratory of Large Animal Models for BiomedicineGuangdong Provincial Key Laboratory of Large Animal Models for BiomedicineBrain organoids have been considered as an advanced platform for in vitro disease modeling and drug screening, but numerous roadblocks exist, such as lack of large-scale production technology and lengthy protocols with multiple manipulation steps, impeding the industrial translation of brain organoid technology. Here, we describe the high-speed and large-scale production of midbrain organoids using a high-throughput screening-compatible platform within 30 days. Micro midbrain organoids (µMOs) exhibit a highly uniform morphology and gene expression pattern with minimal variability. Notably, µMOs show dramatically accelerated maturation, resulting in the generation of functional µMOs within only 30 days of differentiation. Furthermore, individual µMOs display highly consistent responsiveness to neurotoxin, suggesting their usefulness as an in vitro high-throughput drug toxicity screening platform. Collectively, our data indicate that µMO technology could represent an advanced and robust platform for in vitro disease modeling and drug screening for human neuronal diseases.http://dx.doi.org/10.1155/2023/3320211
spellingShingle Xuerui Yao
Ji Hyun Kang
Kee-Pyo Kim
Hyogeun Shin
Zhe-Long Jin
Hao Guo
Yong-Nan Xu
Ying-Hua Li
Sai Hali
Jeongwoo Kwon
Hyeonwoo La
Chanhyeok Park
Yong-June Kim
Lin Wang
Kwonho Hong
Qilong Cao
Il-Joo Cho
Nam-Hyung Kim
Dong Wook Han
Production of Highly Uniform Midbrain Organoids from Human Pluripotent Stem Cells
Stem Cells International
title Production of Highly Uniform Midbrain Organoids from Human Pluripotent Stem Cells
title_full Production of Highly Uniform Midbrain Organoids from Human Pluripotent Stem Cells
title_fullStr Production of Highly Uniform Midbrain Organoids from Human Pluripotent Stem Cells
title_full_unstemmed Production of Highly Uniform Midbrain Organoids from Human Pluripotent Stem Cells
title_short Production of Highly Uniform Midbrain Organoids from Human Pluripotent Stem Cells
title_sort production of highly uniform midbrain organoids from human pluripotent stem cells
url http://dx.doi.org/10.1155/2023/3320211
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