Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/105238
Title: Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
Authors: Segal, Joe M.
No, Da Yoon
Saeb-Parsy, Kourosh
Serra, Maria Paola
Horcas-Lopez, Marta
Mastoridis, Sotiris
Jassem, Wayel
Frank, Curtis W.
Nakauchi, Hiromitsu
Glenn, Jeffrey S.
S. Tamir Rashid
Ng, Soon Seng
Blackford, Samuel J. I.
Cho, Nam Joon
Keywords: DRNTU::Science::Biological sciences
Biomimetic Materials
Liver Stem Cells
Issue Date: 2018
Source: Ng, S. S., Saeb-Parsy, K., Blackford, S. J. I., Segal, J. M., Serra, M. P., Horcas-Lopez, M., . . . S. Tamir Rashid. (2018). Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold. Biomaterials, 182, 299-311. doi:10.1016/j.biomaterials.2018.07.043
Series/Report no.: Biomaterials
Abstract: 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.
URI: https://hdl.handle.net/10356/105238
http://hdl.handle.net/10220/47896
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2018.07.043
Rights: © 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:MSE Journal Articles

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