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

Soon Seng Ng, Kourosh Saeb-Parsy, Joe M. Segal, Maria Paola Serra, Samuel J.I. Blackford, Marta Horcas Lopez, Da Yoon No, Curtis W. Frank, Nam Joon Cho, Hiromitsu Nakauchi, Jeffrey S. Glenn, S. Tamir Rashid

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)
128 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)299-311
JournalBiomaterials
Volume182
Issue number0
Early online date27 Jul 2018
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

  • Biomimetic materials
  • Liver stem cells
  • Bioengineering
  • Organogenesis

Fingerprint

Dive into the research topics of 'Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold'. Together they form a unique fingerprint.

Cite this