ENHANCE · Engineering the 3D Niche to enHANCE functionality of hepatocytes derived from human iPSCs

Engineering the 3D Niche to enHANCE functionality of hepatocytes derived from human iPSCs

Liver disease is a growing clinical burden, resulting in over 100,000 deaths and around 6,000 liver transplants each year in Europe. Where there is the possibility of natural regeneration of the liver, auxiliary liver transplantation with a small amount of donor tissue can support hepatic function during recovery. However, the availability of liver transplantation therapies is now severely limited by insufficient organ donation, and similarly the supply of primary human hepatocytes is very restricted and since these cells cannot be easily expanded in vitro while retaining their characteristics. Hepatocytes derived from human induced pluripotent stem cells (i-Heps) afford us the exciting possibility of redressing these growing shortages, and heralding in a new era of patient specific drug and disease modelling. Clinical applications are restricted by their poor in vivo functionality, in comparison with the gold standard-freshly isolated primary hepatocytes. This insufficiency, due largely to incomplete maturation, also limits their usefulness for other target applications such as in vitro disease modelling, drug, toxicology, and developmental studies. One of the major reasons for this failure is the lack of a systematic approach, empirically defining a signature of maturity that must be reached in order for i-Heps to cross a threshold of usefulness. Emerging evidence suggests the three dimensional environment surrounding a cell (the niche) critically influences cellular function. The objective of ENHANCE was to identify relevant factors from the extracellular niche which promote i-Heps function in 3D and use this technology to generate functionally optimised i-Heps constructs suitable for clinical transplantation.

Data: CORDIS, © European Union