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SUMMARY:Bioengineering human liver organoids using induced-pluripotent ste
 m cells in 3D hydrogel - Dr Soon Seng Ng\, King’s College London
DTSTART:20180601T130000Z
DTEND:20180601T140000Z
UID:TALK104047@talks.cam.ac.uk
CONTACT:Hilde Hambro
DESCRIPTION:Generation of human organoids from induced pluripotent stem ce
 lls (iPSCs) offers exciting possibilities for developmental biology\, dise
 ase modelling and cell therapy. Significant advances towards those goals h
 ave 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 full
 y defined liver organoid platform using inverted colloid crystal (ICC) who
 se 3-dimensional mechanical properties could be engineered to recapitulate
  the extracellular niche sensed by hepatic progenitors during human develo
 pment. iPSC derived hepatic progenitors (IH) formed organoids most optimal
 ly in ICC scaffolds constructed with 140 µm diameter pores coated with Co
 llagen in a two-step process mimicking liver bud formation. The resultant 
 organoids were closer to adult tissue\, compared to 2D and 3D controls\, w
 ith respect to morphology\, gene expression\, protein secretion\, drug met
 abolism and viral infection and could integrate\, vascularize and function
  following implantation into livers of immune-deficient mice. Preliminary 
 interrogation of the underpinning mechanisms highlighted the importance of
  TGF and hedgehog signalling pathways. The combination of functional re
 levance with tuneable mechanical properties leads us to propose this bioen
 gineered platform to be ideally suited for a range of future mechanistic a
 nd clinical organoid related applications. 
LOCATION:Oatley Seminar Room\, Department of Engineering
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