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CATEGORIES:Engineering - Mechanics and Materials Seminar Seri
 es
SUMMARY:Bioengineering human liver organoids using induced
 -pluripotent stem cells in 3D hydrogel - Dr Soon S
 eng Ng\, King’s College London
DTSTART;TZID=Europe/London:20180601T140000
DTEND;TZID=Europe/London:20180601T150000
UID:TALK104047AThttp://talks.cam.ac.uk
URL:http://talks.cam.ac.uk/talk/index/104047
DESCRIPTION:Generation of human organoids from induced pluripo
 tent stem cells (iPSCs) offers exciting possibilit
 ies for developmental biology\, disease modelling 
 and cell therapy. Significant advances towards tho
 se goals have been hampered by dependence on anima
 l derived matrices (e.g. Matrigel)\, immortalized 
 cell lines and resultant structures that are diffi
 cult to control or scale. To address these challen
 ges\, we aimed to develop a fully defined liver or
 ganoid platform using inverted colloid crystal (IC
 C) whose 3-dimensional mechanical properties could
  be engineered to recapitulate the extracellular n
 iche sensed by hepatic progenitors during human de
 velopment. iPSC derived hepatic progenitors (IH) f
 ormed organoids most optimally in ICC scaffolds co
 nstructed with 140 µm diameter pores coated with C
 ollagen in a two-step process mimicking liver bud 
 formation. The resultant organoids were closer to 
 adult tissue\, compared to 2D and 3D controls\, wi
 th respect to morphology\, gene expression\, prote
 in secretion\, drug metabolism and viral infection
  and could integrate\, vascularize and function fo
 llowing implantation into livers of immune-deficie
 nt mice. Preliminary interrogation of the underpin
 ning mechanisms highlighted the importance of TGF
  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 futur
 e mechanistic and clinical organoid related applic
 ations. 
LOCATION:Oatley Seminar Room\, Department of Engineering
CONTACT:Hilde Hambro
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