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

Author

Listed:
  • Ann-Na Cho

    (Yonsei University)

  • Yoonhee Jin

    (Yonsei University)

  • Yeonjoo An

    (Yonsei University)

  • Jin Kim

    (Yonsei University)

  • Yi Sun Choi

    (Yonsei University)

  • Jung Seung Lee

    (Yonsei University)

  • Junghoon Kim

    (Yonsei University)

  • Won-Young Choi

    (Yonsei University)

  • Dong-Jun Koo

    (Seoul National University)

  • Weonjin Yu

    (Duke-NUS Medical School)

  • Gyeong-Eon Chang

    (Yonsei University)

  • Dong-Yoon Kim

    (Seoul National University)

  • Sung-Hyun Jo

    (Soongsil University)

  • Jihun Kim

    (Yonsei University College of Medicine)

  • Sung-Yon Kim

    (Seoul National University
    Seoul National University)

  • Yun-Gon Kim

    (Soongsil University)

  • Ju Young Kim

    (Kangwon National University)

  • Nakwon Choi

    (Korea Institute of Science and Technology (KIST))

  • Eunji Cheong

    (Yonsei University)

  • Young-Joon Kim

    (Yonsei University)

  • Hyunsoo Shawn Je

    (Duke-NUS Medical School)

  • Hoon-Chul Kang

    (Yonsei University College of Medicine)

  • Seung-Woo Cho

    (Yonsei University
    Institute for Basic science (IBS)
    Yonsei University)

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.

Suggested Citation

  • 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, 2021. "Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids," Nature Communications, Nature, vol. 12(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24775-5
    DOI: 10.1038/s41467-021-24775-5
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    Cited by:

    1. Dohui Kim & Hyeonji Lim & Jaeseung Youn & Tae-Eun Park & Dong Sung Kim, 2024. "Scalable production of uniform and mature organoids in a 3D geometrically-engineered permeable membrane," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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