Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson's disease modeling

Tae Hwan Kwak; Ji Hyun Kang; Sai Hali; Jonghun Kim; Kee Pyo Kim; Chanhyeok Park; Ju Hyun Lee; Ha Kyun Ryu; Ji Eun Na; Junghyun Jo; Hyunsoo Shawn Je; Huck Hui Ng; Jeongwoo Kwon; Nam Hyung Kim; Kwon Ho Hong; Woong Sun; Chi Hye Chung; Im Joo Rhyu; Dong Wook Han

doi:10.1002/stem.3163

Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson's disease modeling

Tae Hwan Kwak, Ji Hyun Kang, Sai Hali, Jonghun Kim, Kee Pyo Kim, Chanhyeok Park, Ju Hyun Lee, Ha Kyun Ryu, Ji Eun Na, Junghyun Jo, Hyunsoo Shawn Je, Huck Hui Ng, Jeongwoo Kwon, Nam Hyung Kim, Kwon Ho Hong, Woong Sun, Chi Hye Chung, Im Joo Rhyu, Dong Wook Han

Department of Biomedicine & Health Science

Research output: Contribution to journal › Article › peer-review

80 Scopus citations

Abstract

Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells, including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson's disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD.

Original language	English
Pages (from-to)	727-740
Number of pages	14
Journal	Stem Cells
Volume	38
Issue number	6
DOIs	https://doi.org/10.1002/stem.3163
State	Published - 1 Jun 2020

Bibliographical note

Funding Information:
This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (NRF-2016R1A2B3011860, NRF-2017M3C7A1047640) and by a grant from the Next-Generation BioGreen 21 Program (PJ01322101), Rural Development Administration, Republic of Korea.

Publisher Copyright:
©AlphaMed Press 2020

Keywords

differentiation
embryonic stem cells (ESCs)
neural differentiation
Parkinson's disease

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/stem.3163

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Kwak, T. H., Kang, J. H., Hali, S., Kim, J., Kim, K. P., Park, C., Lee, J. H., Ryu, H. K., Na, J. E., Jo, J., Je, H. S., Ng, H. H., Kwon, J., Kim, N. H., Hong, K. H., Sun, W., Chung, C. H., Rhyu, I. J., & Han, D. W. (2020). Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson's disease modeling. Stem Cells, 38(6), 727-740. https://doi.org/10.1002/stem.3163

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title = "Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson's disease modeling",

abstract = "Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells, including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson's disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD.",

keywords = "differentiation, embryonic stem cells (ESCs), neural differentiation, Parkinson's disease",

author = "Kwak, {Tae Hwan} and Kang, {Ji Hyun} and Sai Hali and Jonghun Kim and Kim, {Kee Pyo} and Chanhyeok Park and Lee, {Ju Hyun} and Ryu, {Ha Kyun} and Na, {Ji Eun} and Junghyun Jo and Je, {Hyunsoo Shawn} and Ng, {Huck Hui} and Jeongwoo Kwon and Kim, {Nam Hyung} and Hong, {Kwon Ho} and Woong Sun and Chung, {Chi Hye} and Rhyu, {Im Joo} and Han, {Dong Wook}",

note = "Funding Information: This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (NRF-2016R1A2B3011860, NRF-2017M3C7A1047640) and by a grant from the Next-Generation BioGreen 21 Program (PJ01322101), Rural Development Administration, Republic of Korea. Publisher Copyright: {\textcopyright}AlphaMed Press 2020",

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Kwak, TH, Kang, JH, Hali, S, Kim, J, Kim, KP, Park, C, Lee, JH, Ryu, HK, Na, JE, Jo, J, Je, HS, Ng, HH, Kwon, J, Kim, NH, Hong, KH, Sun, W, Chung, CH, Rhyu, IJ & Han, DW 2020, 'Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson's disease modeling', Stem Cells, vol. 38, no. 6, pp. 727-740. https://doi.org/10.1002/stem.3163

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T1 - Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson's disease modeling

AU - Kwak, Tae Hwan

AU - Kang, Ji Hyun

AU - Hali, Sai

AU - Kim, Jonghun

AU - Kim, Kee Pyo

AU - Park, Chanhyeok

AU - Lee, Ju Hyun

AU - Ryu, Ha Kyun

AU - Na, Ji Eun

AU - Jo, Junghyun

AU - Je, Hyunsoo Shawn

AU - Ng, Huck Hui

AU - Kwon, Jeongwoo

AU - Kim, Nam Hyung

AU - Hong, Kwon Ho

AU - Sun, Woong

AU - Chung, Chi Hye

AU - Rhyu, Im Joo

AU - Han, Dong Wook

N1 - Funding Information: This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (NRF-2016R1A2B3011860, NRF-2017M3C7A1047640) and by a grant from the Next-Generation BioGreen 21 Program (PJ01322101), Rural Development Administration, Republic of Korea. Publisher Copyright: ©AlphaMed Press 2020

PY - 2020/6/1

Y1 - 2020/6/1

N2 - Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells, including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson's disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD.

AB - Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells, including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson's disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD.

KW - differentiation

KW - embryonic stem cells (ESCs)

KW - neural differentiation

KW - Parkinson's disease

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U2 - 10.1002/stem.3163

DO - 10.1002/stem.3163

M3 - Article

C2 - 32083763

AN - SCOPUS:85081244198

SN - 1066-5099

VL - 38

SP - 727

EP - 740

JO - Stem Cells

JF - Stem Cells

IS - 6

ER -

Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson's disease modeling

Abstract

Bibliographical note

Keywords

UN SDGs

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