iPSC-derived Hepatocytes as Platforms for Research in Viral Hepatitis and Non-alcoholic Steatohepatitis

Funding Type: 
Tissue Collection for Disease Modeling
Grant Number: 
Award Value: 
Disease Focus: 
Liver Disease
Infectious Disease
Stem Cell Use: 
iPS Cell
Public Abstract: 

Hepatitis C and fatty liver disease are the two most common liver diseases in California. Individuals from different backgrounds are susceptible to these liver diseases, but they have unique genetic profiles that may influence the severity of disease and the response to specific therapies. Technology now makes it possible to generate stem cells from a person’s own skin. These cells can subsequently be used to generate liver cells identical to those from the original donor. Using this approach, scientists can perform research directly on an individual’s own liver cells to identify features that make the cells susceptible or resistant to disease and drug therapy. In this project, the research team will collect blood and skin tissue from people with liver disease and from healthy control subjects. The donated tissues will be placed in a "bank" for the production of stem cells. The overall goal is for the donated cells to be made available to scientists who will convert them to liver cells, and then carefully study them to learn more about liver disease. Research such as this is extremely valuable because it allows patients and volunteers to make a very personal contribution to the understanding of liver disease. The materials donated to this tissue "bank" will be a resource to the scientific community for many years.

Statement of Benefit to California: 

Hepatitis C and fatty liver disease are the two most common liver diseases affecting the citizens of California. Together they afflict one in every 12 people in the state and kill roughly 4,000 state residents each year. Researchers in California are actively seeking new information about the causes of and treatments for liver disease; their progress will be greatly accelerated by the opportunity to directly study the biology of diseased patients. The goal of this project is to build a "bank" of stem cells from local patients with liver disease. Patient donors will come from many different backgrounds, reflecting the great diversity of California. The bank, once established, will be a tremendous resource for medical research because the banked cells will be renewable and made available to the entire research community. Banked stem cells will enable researchers to study the genetics and biology of liver disease and to test new therapies. Importantly, they will give researchers an opportunity to study liver disease in its most important context - the affected patient. The research made possible through this effort will greatly enhance our understanding of liver disease; this will in turn reduce the negative impact of liver disease on the health and well-being of California residents.

Progress Report: 

The goal of this project is to collect blood or skin tissues from subjects with liver disease to learn more about the factors that predispose individuals to their conditions. We are focusing our attention on subjects with two specific liver diseases: hepatitis C and non-alcoholic steatohepatitis (the latter is termed "NASH" or "fatty liver disease"). These are the two most common causes of liver disease in California. In the case of hepatitis C, research to date shows that factors such as race, genetic makeup and immunologic makeup influence individual responses to infection by the hepatitis C virus as well as responses to antiviral drug treatment. Our goal is to recruit individuals with diverse backgrounds and responses to hepatitis C infection and treatment, to enable scientists to identify the determinants of susceptibility or resistance to hepatitis C-related liver disease. In the case of fatty liver disease, we are recruiting subjects who have significant liver injury due to the accumulation of fat, proven on a liver biopsy (NASH). NASH is typically found in subjects who are overweight, and who often have additional health problems such as high blood pressure, high cholesterol and diabetes. We are also looking for subjects who are at risk for NASH and have prominent fat accumulation in the liver on a biopsy, but have no evidence of actual liver injury. As with hepatitis C, the goal with fatty liver disease is to accumulate a cohort of subjects with diverse backgrounds and a spectrum of disease severity, to enable scientists to determine the factors that predispose some individuals at risk to serious liver disease while sparing others.