Liver regenerative medicine – towards cell and organoid therapies

Yap K1,2

  1. St Vincent’s Institute, Fitzroy, Victoria.
  2. University of Melbourne Department of Surgery at St Vincent’s Hospital Melbourne, Fitzroy, Victoria.

Liver disease is on the rise, particularly fatty liver disease which is commonly associated with obesity and diabetes. Chronic liver disease often leads to liver failure, which is fatal without a liver transplant. However, liver transplantation simply cannot meet the ongoing increase in demand. Strategies to better understand, diagnose, and treat liver disease are critically required. Our group has an interest in identifying the role and utility of cells within the liver that can contribute to liver regeneration, which can also be harnessed in cell and organoid therapies for liver disease. These include human liver progenitor cells and liver sinusoidal endothelial cells derived from adult human liver, as well as induced pluripotent stem cell (iPSC) produced counterparts. Organoids generated from these cell types have been established in culture and transplanted into a mouse model of liver disease, with demonstration of tissue assembly, functional maturation, and survival in vivo. Comparison between iPSC-derived cells/organoids and human adult liver derived cells/organoids are underway, and recent developments include upscaling of transplantation experiments from mouse to rat, representing a 10-fold increase in scale. It is hoped insights gained from these experiments will guide the development of cell and organoid-based therapies for liver disease.