Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

Ann-Na Cho; Yoonhee Jin; Yeonjoo An; Jin Kim; Yi Sun Choi; Jung Seung Lee; Junghoon Kim; Won-Young Choi; Dong-Jun Koo; Weonjin Yu; Gyeong-Eon Chang; Dong-Yoon Kim; Sung-Hyun Jo; Jihun Kim; Sung-Yon Kim; Yun-Gon Kim; Ju Young Kim; Nakwon Choi; Eunji Cheong; Young-Joon Kim; Hyunsoo Shawn Je; Hoon-Chul Kang; Seung-Woo Cho

doi:10.1038/s41467-021-24775-5

Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

Ann-Na Cho (Co-first Author)
, Yoonhee Jin (Co-first Author)
, Yeonjoo An (Co-first Author)
, Jin Kim
, Yi Sun Choi
, Jung Seung Lee
, Junghoon Kim
, Won-Young Choi
, Dong-Jun Koo
, Weonjin Yu
, Gyeong-Eon Chang
, Dong-Yoon Kim
, Sung-Hyun Jo
, Jihun Kim
, Sung-Yon Kim
, Yun-Gon Kim
, Ju Young Kim
, Nakwon Choi
, Eunji Cheong
, Young-Joon Kim

Hyunsoo Shawn Je, Hoon-Chul Kang, Seung-Woo Cho^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

327 Citations (Scopus)

Abstract

Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases. © The Author(s) 2021.

Original language	English
Article number	4730
Number of pages	23
Journal	Nature Communications
Volume	12
Online published	5 Aug 2021
DOIs	https://doi.org/10.1038/s41467-021-24775-5
Publication status	Published - 2021
Externally published	Yes

Funding

This work was supported by grants from the National Research Foundation of Korea (NRF) (2016M3C9A4921712, 2017M3C7A1047659, 2018M3A9H1021382) funded by the Ministry of Science and ICT (MSIT), Republic of Korea. This work was also supported by Samsung Research Funding & Incubation Center of Samsung Electronics (Project Number SRFC-TC2003-03) and the Institute for Basic Science (IBS-R026-D1). This work was also supported by Singapore National Medical Research Council Open-Fund Individual Research Grant (NMRC/OFIRG/0050/2017) and Singapore National Research Foundation Competitive Research Programme (NRF-CRP17-2017-04).

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This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

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10.1038/s41467-021-24775-5

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Cho, A.-N., Jin, Y., An, Y., Kim, J., Choi, Y. S., Lee, J. S., Kim, J., Choi, W.-Y., Koo, D.-J., Yu, W., Chang, G.-E., Kim, D.-Y., Jo, S.-H., Kim, J., Kim, S.-Y., Kim, Y.-G., Kim, J. Y., Choi, N., Cheong, E., ... Cho, S.-W. (2021). Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids. Nature Communications, 12, Article 4730. https://doi.org/10.1038/s41467-021-24775-5

@article{4c471385a48f4ca69669a7347dbba4dd,

title = "Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids",

abstract = "Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases. {\textcopyright} The Author(s) 2021.",

author = "Ann-Na Cho and Yoonhee Jin and Yeonjoo An and Jin Kim and Choi, \{Yi Sun\} and Lee, \{Jung Seung\} and Junghoon Kim and Won-Young Choi and Dong-Jun Koo and Weonjin Yu and Gyeong-Eon Chang and Dong-Yoon Kim and Sung-Hyun Jo and Jihun Kim and Sung-Yon Kim and Yun-Gon Kim and Kim, \{Ju Young\} and Nakwon Choi and Eunji Cheong and Young-Joon Kim and Je, \{Hyunsoo Shawn\} and Hoon-Chul Kang and Seung-Woo Cho",

year = "2021",

doi = "10.1038/s41467-021-24775-5",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

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Cho, A-N, Jin, Y, An, Y, Kim, J, Choi, YS, Lee, JS, Kim, J, Choi, W-Y, Koo, D-J, Yu, W, Chang, G-E, Kim, D-Y, Jo, S-H, Kim, J, Kim, S-Y, Kim, Y-G, Kim, JY, Choi, N, Cheong, E, Kim, Y-J, Je, HS, Kang, H-C & Cho, S-W 2021, 'Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids', Nature Communications, vol. 12, 4730. https://doi.org/10.1038/s41467-021-24775-5

Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids. / Cho, Ann-Na (Co-first Author); Jin, Yoonhee (Co-first Author); An, Yeonjoo (Co-first Author) et al.
In: Nature Communications, Vol. 12, 4730, 2021.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

AU - Cho, Ann-Na

AU - Jin, Yoonhee

AU - An, Yeonjoo

AU - Kim, Jin

AU - Choi, Yi Sun

AU - Lee, Jung Seung

AU - Kim, Junghoon

AU - Choi, Won-Young

AU - Koo, Dong-Jun

AU - Yu, Weonjin

AU - Chang, Gyeong-Eon

AU - Kim, Dong-Yoon

AU - Jo, Sung-Hyun

AU - Kim, Jihun

AU - Kim, Sung-Yon

AU - Kim, Yun-Gon

AU - Kim, Ju Young

AU - Choi, Nakwon

AU - Cheong, Eunji

AU - Kim, Young-Joon

AU - Je, Hyunsoo Shawn

AU - Kang, Hoon-Chul

AU - Cho, Seung-Woo

PY - 2021

Y1 - 2021

N2 - Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases. © The Author(s) 2021.

AB - Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases. © The Author(s) 2021.

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U2 - 10.1038/s41467-021-24775-5

DO - 10.1038/s41467-021-24775-5

M3 - RGC 21 - Publication in refereed journal

C2 - 34354063

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

M1 - 4730

ER -

Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

Abstract

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Publisher's Copyright Statement

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