Engineering the 3d niche to enhance functionality of hepatocytes derived from human ipscs
Induced pluripotent stem cell derived hepatocytes (i-Heps) afford us the exciting possibility of redressing the growing shortage in liver transplantation tissue and heralding in a new era of patient specific drug and disease modelling. Clinical applications are restricted by their poor functionality in comparison to the gold standard – freshly isolated primary hepatocytes. Emerging evidence suggests the three dimensional environment surrounding a cell (the niche) critically influences cellular function. The objective of ENHANCE is to identify relevant factors from the extracellular niche which promote i-Hep function in 3D and the mechanisms by which they achieve this. This new knowledge will be used to generate functionally optimized i-Hep constructs suitable for clinical transplantation, with proof of concept studies being performed in rodent models of liver failure. This European Fellowship at Kings College London will provide the researcher with advanced training in iPSC technology, i-Hep generation, 2D niche component screening, 3D cell engineering and animal transplantation. A secondment to SME DefiniGEN Ltd will evaluate the feasibility of transfer to a commercial i-Hep production platform as a critical step towards clinical trials.