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 KimHyunsoo Shawn Je, Hoon-Chul Kang, Seung-Woo Cho

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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.
Original languageEnglish
Article number4730
Pages (from-to)1-23
Number of pages23
JournalNature Communications
Volume12
DOIs
Publication statusPublished - 5 Aug 2021
Externally publishedYes

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Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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