Cited by 5053D Printing in Biomedical ResearchCancer Cells and MetastasisTissue Engineering and Regenerative Medicine

Tissue geometry drives deterministic organoid patterning

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Gjorevski, N., Nikolaev, M., Brown, T. E., Mitrofanova, O., Brandenberg, N., DelRio, F. W., Yavitt, F. M., Liberali, P. +2 more·2022·Science

Abstract

Spatial and temporal organoid control: Stem cell–derived organoids form through self-organization and serve as models for organ development, function, and disease, with potential applications in drug development and personalized medicine. However, in the absence of external guidance, developmental processes are stochastic, resulting in variable end products that differ significantly from the native organ. Gjorevski et al . developed approaches for specifying the initial organoid geometry to build intestinal organoids of defined shape, size, and cell distributions, forming structures that are predictable, more similar to normal organs, and reproducible (see the Perspective by Huycke and Gartner). These methods identify symmetry-breaking mechanisms in intestinal morphogenesis and have potential for standardizing organoid-based therapies and facilitating the refinement of mechanistic studies. —BAP

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  • Dextran-based GMP-compatible hydrogels support cell expansion over longer passages.

    “while dextran-based GMP-compatible hydrogels support expansion of cells for longer passages69.”

    From Organoids (2022) · cites this paper as [69]

    The paper describes PEG-based hydrogels and collagen–Matrigel scaffolds, not dextran-based hydrogels (Abstract; page unavailable). Searches for dextran, GMP compatibility, and extended passaging found no passage establishing the attributed claim. (LLM, conf=0.76)

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  • Organoids of murine intestines, livers, and pancreas were successfully transplanted into mice, and the transplanted organoids could restore organ dysfunction.

    “Organoids of murine intestines31, livers35,125,126 and pancreas69,146 were successfully transplanted into mice, and the transplanted organoids could restore organ dysfunction.”

    From Organoids (2022) · cites this paper as [69]

    The paper’s Abstract describes engineering and patterning intestinal organoids in culture, not transplanting them into mice. Searches for transplantation and restoration of organ function found no passage reporting either outcome. The liver and pancreas citations in the citing sentence are separate from this source. (LLM, conf=0.76)

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  • Human pancreas organoids, intestinal organoids and colorectal cancer organoids could grow in a dextran-based fully defined ECM, but would not expand long term.

    “In that regard, some advances were shown with human pancreas organoids, intestinal organoids and colorectal cancer organoids, which could grow in a dextran-based fully defined ECM; however, they would not expand long term3,69.”

    From Organoids (2022) · cites this paper as [69]

    The experimental passages in our copy describe intestinal organoids in PEG-based hydrogels and in collagen–Matrigel hydrogels (section labeled Abstract; page unavailable). Searches for dextran, pancreatic and colorectal cancer organoids, and long-term expansion found no passage addressing whether the three organoid types could grow in a dextran-based fully defined ECM but could not expand long term. (LLM, conf=0.75)

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Authors
Gjorevski, N., Nikolaev, M., Brown, T. E., Mitrofanova, O., Brandenberg, N., DelRio, F. W., Yavitt, F. M., Liberali, P., Anseth, K. S., & Lutolf, M. P.
Affiliations
  • École Polytechnique Fédérale de Lausanne (CH)
  • University of Colorado Boulder (US)
  • Material, Physical, and Chemical Sciences Center, Sandia National Laboratories, Albuquerque, NM 87185, USA.
  • Friedrich Miescher Institute (CH)
  • Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Corresponding author
  • Gjorevski, N.
  • Nikolaev, M.
  • Brown, T. E.
Venue
Science
Published
2022-01-07
Volume
375
Issue
6576
Pages
eaaw9021-eaaw9021
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W4205165375
Cited by
505
References
50
Citations by year
2026: 93 · 2025: 125 · 2024: 116 · 2023: 93 · 2022: 77 · 2021: 1
FWCI
30.15
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (179447, 310030)
  • National Institute of General Medical Sciences (T32GM065103)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK120921)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
intestinal organoids, tissue geometry, crypt formation, stem cell niche
MeSH terms
YAP-Signaling Proteins, Animals, Cell Differentiation, Epithelial Cells, Intestinal Mucosa, Organoids, Stem Cells, Signal Transduction, Paneth Cells, Hydrogels, Tissue Engineering, Organogenesis, Tissue Culture Techniques, Cell Shape, Mice, Receptors, Notch

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