Cited by 397Pluripotent Stem Cells Research3D Printing in Biomedical ResearchNeurogenesis and neuroplasticity mechanisms

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

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Cho, Ann-Na, Jin, Yoonhee, An, Yeonjoo, Kim, Jin, Choi, Yi Sun, Lee, Jung Seung, Kim, Junghoon, Choi, Won-Young +15 more·2021·Nature Communications

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.

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  • Many other organoid models, including brain, intestinal, mammary gland, and retinal organoids, employ 3D ECM-based hydrogels to induce complex tissue architecture that cannot be achieved in ECM-free floating culture.

    “While many other organoid models, including brain[13], intestinal [14], mammary gland [15], and retinal organoids [16], employ 3D ECM-based hydrogels to induce complex tissue architecture that cannot be achieved in ECM-free floating culture, the same has not been explored for skin yet.”

    From Efficient Generation of Skin Organoids from Pluripotent Cells via Defined Extracellular Matrix Cues and Morphogen Gradients in a Spindle‐Shaped Microfluidic Device (2024) · cites this paper as [13]

    The Results describe embedding brain organoids in a 3D ECM hydrogel, and the Discussion reports more complex brain-like structures with the ECM–microfluidic platform. The paper does not establish that those structures cannot be achieved in ECM-free floating culture; the reported platform also combines the hydrogel with microfluidics. Citation [13] is attached to the brain-organoid example, not the other organoid types. (LLM, conf=0.85)

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Authors
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., Kim, Y.-J., Je, H. S., Kang, H.-C., & Cho, S.-W.
Affiliations
  • Yonsei University (KR)
  • Kangwon National University (KR)
  • Seoul National University (KR)
  • Duke-NUS Medical School (SG)
  • Soongsil University (KR)
  • Korea Institute of Science and Technology (KR)
Corresponding author
Cho, Seung-Woo
Venue
Nature Communications
Published
2021-08-05
Volume
12
Issue
1
Pages
4730-4730
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3188744629
Cited by
397
References
91
Citations by year
2026: 77 · 2025: 83 · 2024: 96 · 2023: 66 · 2022: 69 · 2021: 6
FWCI
18.60
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Funders
  • National Research Foundation of Korea (2016M3C9A4921712, 2017M3C7A1047659, 2018M3A9H1021382)
  • Institute for Basic Science (IBS-R026-D1)
  • Samsung (SRFC-TC2003-03)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
brain organoids, microfluidics, brain extracellular matrix, induced pluripotent stem cells, neurogenesis, organoid maturation, dynamic culture, periodic flow, electrophysiological function, 3D cell culture
MeSH terms
Animals, Brain, Culture Media, Extracellular Matrix, Feasibility Studies, Humans, Models, Anatomic, Models, Neurological, Neuroglia, Organ Culture Techniques, Organoids, Swine, Hydrogels, Gene Expression Profiling, Neurogenesis, Electrophysiological Phenomena, Lab-On-A-Chip Devices, Induced Pluripotent Stem Cells

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