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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Ng, Soon Seng 
Saeb-Parsy, Kourosh  ORCID logo  https://orcid.org/0000-0002-0633-3696
Blackford, Samuel JI 
Segal, Joe M 
Serra, Maria Paola 

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.

Description

Keywords

Bioengineering, Biomimetic materials, Liver stem cells, Organogenesis, Biocompatible Materials, Cells, Cultured, Crystallization, Humans, Induced Pluripotent Stem Cells, Liver, Organoids, Polyethylene Glycols, Tissue Engineering, Tissue Scaffolds

Journal Title

Biomaterials

Conference Name

Journal ISSN

0142-9612
1878-5905

Volume Title

182

Publisher

Elsevier BV