Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/89834
Title: Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
Authors: Blackford, Samuel J. I.
Ng, Soon Seng
Saeb-Parsy, Kourosh
Segal, Joe M.
Serra, Maria Paola
Horcas-Lopez, Marta
No, Da Yoon
Mastoridis, Sotiris
Jassem, Wayel
Frank, Curtis W.
Cho, Nam Joon
Nakauchi, Hiromitsu
Glenn, Jeffrey S.
Rashid, S. Tamir
Keywords: Biomimetic Materials
Liver Stem Cells
DRNTU::Engineering::Materials::Biomaterials
Issue Date: 2018
Source: Ng, S. S., Saeb-Parsy, K., Blackford, S. J., Segal, J. M., Serra, M. P., Horcas-Lopez, M., . . . Rashid, S. T. (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/10356/89834
http://hdl.handle.net/10220/46368
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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