Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids
Open accessAbstract
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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Li, Z., Li, Q., Zhou, C., Lu, K., Liu, Y., Xuan, L., & Wang, X. (2023) · Biomicrofluidics · doi:10.1063/5.0171350 · Cited by 33 · see citing works
Saglam‐Metiner, P., Yıldırım, E., Dincer, C., Başak, O., & Yeşil-Çeliktaş, Ö. (2024) · Microchimica Acta · doi:10.1007/s00604-023-06165-4 · Cited by 36 · see citing works
Models of Herpes Simplex Virus Latency
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In situ biosensing technologies for an organ-on-a-chip
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Self-citationPramotton, F. M., Spitz, S., & Kamm, R. D. (2024) · Advanced Science · doi:10.1002/advs.202403892 · Cited by 33 · see citing works
Kim, S., Choi, Y. S., Lee, J. S., Jo, S.-H., Kim, Y., & Cho, S. (2021) · Journal of Industrial and Engineering Chemistry · doi:10.1016/j.jiec.2021.11.044 · Cited by 32 · see citing works
Self-citationNanoscale surface coatings and topographies for neural interfaces
Cho, Y., Choi, Y., & Seong, H. (2023) · Acta Biomaterialia · doi:10.1016/j.actbio.2023.12.025 · Cited by 32 · see citing works
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A dive into the bath: embedded 3D bioprinting of freeform in vitro models
Öztürk-Öncel, M. Ö., Leal-Martínez, B. H., Monteiro, R. F., Gomes, M. E., & Domingues, R. M. A. (2023) · Biomaterials Science · doi:10.1039/d3bm00626c · Cited by 32 · see citing works
Advances in gut–brain organ chips
Zhang, Y., Lu, S., Zhuang, J., & Liang, L. (2024) · Cell Proliferation · doi:10.1111/cpr.13724 · Cited by 27 · see citing works
Ma, W., Zheng, Y., Yang, G.-Z., Zhang, H., Lu, M., Ma, H., Wu, C., & Lu, H. (2024) · Materials Horizons · doi:10.1039/d4mh00228h · Cited by 27 · see citing works
- 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
- ORCID
- Venue
- Nature Communications
- Published
- 2021-08-05
- Volume
- 12
- Issue
- 1
- Pages
- 4730-4730
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC8342542
- 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
- gold
- doi.org
- 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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