Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold

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 ce...

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Main 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
Other Authors: School of Materials Science & Engineering
Format: Article
Language:English
Published: 2019
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Online Access:https://hdl.handle.net/10356/105238
http://hdl.handle.net/10220/47896
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1052382023-07-14T15:56:16Z Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold 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 School of Materials Science & Engineering DRNTU::Science::Biological sciences Biomimetic Materials Liver Stem Cells 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. NRF (Natl Research Foundation, S’pore) Published version 2019-03-25T07:12:43Z 2019-12-06T21:47:50Z 2019-03-25T07:12:43Z 2019-12-06T21:47:50Z 2018 Journal Article 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 0142-9612 https://hdl.handle.net/10356/105238 http://hdl.handle.net/10220/47896 10.1016/j.biomaterials.2018.07.043 en Biomaterials © 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/). 13 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
Biomimetic Materials
Liver Stem Cells
spellingShingle DRNTU::Science::Biological sciences
Biomimetic Materials
Liver Stem Cells
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
Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
description 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.
author2 School of Materials Science & Engineering
author_facet School of Materials Science & Engineering
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
format Article
author 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
author_sort Segal, Joe M.
title Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
title_short Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
title_full Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
title_fullStr Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
title_full_unstemmed Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
title_sort human ips derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
publishDate 2019
url https://hdl.handle.net/10356/105238
http://hdl.handle.net/10220/47896
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