Guided self-organization and cortical plate formation in human brain organoids
Open accessAbstract
Three-dimensional cell culture models have either relied on the self-organizing properties of mammalian cells or used bioengineered constructs to arrange cells in an organ-like configuration. While self-organizing organoids excel at recapitulating early developmental events, bioengineered constructs reproducibly generate desired tissue architectures. Here, we combine these two approaches to reproducibly generate human forebrain tissue while maintaining its self-organizing capacity. We use poly(lactide-co-glycolide) copolymer (PLGA) fiber microfilaments as a floating scaffold to generate elongated embryoid bodies. Microfilament-engineered cerebral organoids (enCORs) display enhanced neuroectoderm formation and improved cortical development. Furthermore, reconstitution of the basement membrane leads to characteristic cortical tissue architecture, including formation of a polarized cortical plate and radial units. Thus, enCORs model the distinctive radial organization of the cerebral cortex and allow for the study of neuronal migration. Our data demonstrate that combining 3D cell culture with bioengineering can increase reproducibility and improve tissue architecture.
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Brain organoids derived from iPSCs develop in culture along a trajectory mimicking key features of fetal brain development and can be patterned toward specific brain regions affected in tauopathy.
“Brain organoids derived from iPSCs develop in culture along a trajectory mimicking key features of fetal brain development and can be patterned toward specific brain regions affected in tauopathy (Camp et al., 2015; Lancaster et al., 2017; Paşca et al., 2015; Velasco et al., 2019; Yoon et al., 2019).”
From ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids (2021) · cites this paper as Lancaster et al., 2017
The Online Methods (Preparation of EBs and enCORs) include an iPS cell line, and the main text reports that engineered organoids form forebrain tissue, including regions consistent with hippocampal identity. It also finds that 60-day organoids most closely match early-gestation human forebrain gene expression. The copy does not establish a developmental trajectory matching fetal brain development or connect the patterned regions to tauopathy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe advantages of the scaffold primarily stem from the increased surface-to-volume ratio.
“These advantages primarily stem from the increased surface-to-volume ratio, aligning with previous studies that used fibers to guide organoid development and improve surface-to-volume dynamics (68).”
From Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human cortical organoid microphysiological systems (2025) · cites this paper as [68]
Previously established protocols reproducibly generate human telencephalon organoids.
“We used previously established protocols that reproducibly generate human telencephalon organoids23,24 (Extended Data Fig. 5a–c).”
From Single-cell brain organoid screening identifies developmental defects in autism (2023) · cites this paper as [23]
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- Authors
- Lancaster, M. A., Corsini, N. S., Wolfinger, S., Gustafson, E. H., Phillips, A. W., Burkard, T. R., Otani, T., Livesey, F. J., & Knoblich, J. A.
- Affiliations
- Institute of Molecular Biotechnology (AT)
- University of Cambridge (GB)
- Corresponding author
- Lancaster, Madeline A
- Knoblich, Juergen A
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2017-05-31
- Volume
- 35
- Issue
- 7
- Pages
- 659-666
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC5824977
- OpenAlex
- W2617770907
- Cited by
- 783
- References
- 14
- Citations by year
- 2026: 58 · 2025: 72 · 2024: 83 · 2023: 101 · 2022: 104 · 2021: 119 · 2020: 103 · 2019: 75 · 2018: 52 · 2017: 16
- FWCI
- 28.48
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-10-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (101052/Z/13/Z)
- Medical Research Council (MR/L023784/2, MR/L023784/1)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- brain organoids, embryoid bodies, neuronal migration, forebrain development, 3D cell culture, reproducibility
- MeSH terms
- Cells, Cultured, Humans, Organ Culture Techniques, Organoids, Prosencephalon, Tissue Engineering, Guided Tissue Regeneration, Neurogenesis, Neural Stem Cells, Batch Cell Culture Techniques
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