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Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
Open accessAbstract
Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development. iPSC derived hepatic progenitors (IH) formed organoids most optimally in ICC scaffolds constructed with 140 μm diameter pores coated with type I collagen in a two-step process mimicking liver bud formation. The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularise and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFβ and hedgehog signalling pathways. The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications.
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“Cell-binding cues from collagen, fibronectin, or laminin have frequently been added to synthetic hydrogels to allow for organoid growth and differentiation.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [158]
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“Attachment of human iPSCs was successful in assemblies functionalized with collagen I and laminin-521 but not with fibronectin.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [158]
In the citing paper
“Ng and colleagues created functional human liver organoids derived from human iPSCs in a colloidal crystal of PEG functionalized with collagen I, fibronectin, or laminin-521158,159.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [158]
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Metadata
- Authors
- Ng, S. S., Saeb-Parsy, K., Blackford, S. J. I., Segal, J. M., Serra, M. P., Horcas-Lopez, M., No, D. Y., Mastoridis, S., Jassem, W., Frank, C. W., Cho, N. J., Nakauchi, H., Glenn, J. S., & Rashid, S. T.
- Affiliations
- King's College London (GB)
- Stanford Medicine (US)
- Stanford University (US)
- Nanyang Technological University (SG)
- Corresponding author
- Glenn, Jeffrey S.
- Rashid, S. Tamir
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 182
- Pages
- 299-311
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC6131727
- OpenAlex
- W2883652711
- Cited by
- 133
- References
- 31
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 14 · 2023: 19 · 2022: 18 · 2021: 26 · 2020: 23 · 2019: 9 · 2018: 3
- FWCI
- 15.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biomaterials (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- DR-NTU (Nanyang Technological University) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- National Institute for Health Research (NIHR), United Kingdom
- Guy's and St Thomas' NHS Foundation Trust, United Kingdom
- NIHR Biomedical Research, United Kingdom
- Medical Research Council (MRC) (MGSBACR), United Kingdom
- Alpha-1 Antitrypsin Foundation, United Kingdom
- National Institutes of Health (R01AI099245, U19AI109662)
- Burroughs Wellcome Fund
- California Institute for Regenerative Medicine (LA1_C12-06917)
- National Research Foundation of Singapore (NRF-CRP10-2012-07)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- liver organoids, induced pluripotent stem cells, polyethylene glycol, type I collagen coating, scaffold mechanical properties, TGF-beta signaling, Hedgehog signaling, drug metabolism, disease modeling
- MeSH terms
- Biocompatible Materials, Cells, Cultured, Crystallization, Humans, Liver, Organoids, Polyethylene Glycols, Tissue Engineering, Tissue Scaffolds, Induced Pluripotent Stem Cells
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