mrp2
Liver Program Progress
Preclinical Development
The goal of our liver program is to develop a cell-based therapeutic product to treat a broad range of liver diseases. Based on promising preclinical proof-of-concept data, we believe that transplantation of hLEC™ human liver engrafting cells has the potential to restore missing function in diseased or damaged livers. Our initial target indication is liver-based metabolic disorders. We also plan to target additional indications such as acute liver failure and chronic liver disease due to conditions such as hepatitis C.
Learn more about the therapeutic potential of hLEC cells…
Animal Model of Liver Failure
We have obtained rights to a mouse model of liver failure, which has allowed us to test methods for using cell transplantation to repair or regenerate diseased livers. The “FAH knockout mouse,”1 which lacks a key enzyme, FAH (fumaryl-acetoacetate hydrolase), was engineered to mimic a genetically-based fatal human liver disease called tyrosinemia type I. Toxic substances build up in these mice and cause liver damage. This mouse model was developed by Markus Grompe, PhD, of Oregon Health Science University.
In mouse models, we have demonstrated in vivo that our hLEC cells produce FAH, an important protein needed for metabolic function, which is missing in the disease tyrosinemia I.
Collaborations & Grants
StemCells, Inc. has a long history of collaboration with Stanford University in the study of hepatitis C. Hepatitis C is a global health challenge, with approximately 170 million people affected worldwide, and an estimated three million new infections each year.2 The hepatitis C virus (HCV) targets liver cells and is a leading cause of end-stage liver disease. Today, treatment options for HCV remain limited.
In October 2008, we were awarded a $305,000 grant from the National Institute of Diabetes and Digestive and Kidney Diseases (as part of the Small Business Innovation Research (SBIR) Program of the National Institutes of Health (NIH)) to research and develop a potential cell-based therapeutic for liver disease arising from infection by the hepatitis C virus (HCV). In February 2010, we were awarded an additional $98,000 by the NIH as part of the American Recovery and Reinvestment Act to further support this HCV study. The grant is funding ongoing work to investigate whether hLEC can be made resistant to HCV infection, which could address the dual challenges that underlie the disease: preventing infection and restoring lost function of the damaged liver. These studies are being conducted in collaboration with Jeffrey Glenn, MD, Ph.D, Associate Professor of Gastroenterology and Hepatology at Stanford University School of Medicine. Dr. Glenn is a recognized and widely published expert in hepatitis C, and his research has focused on designing novel antiviral strategies.
In March 2001, we were awarded a two year, $300,000 per year SBIR grant from the NIH to fund work in further characterizing the human cells that can be infected by HCV to develop assays for the disease that could lead to the discovery and testing of better therapeutics for the detection, treatment, or prevention of HCV. This work was conducted in collaboration with Dr. Jeffrey Glenn at Stanford University.
Continue learning more about hLEC cells…
Back to Liver Program main page.
- Hisaya Azuma, Nicole Paulk, Aarati Ranade, Craig Dorrell, Muhsen Al-Dhalimy, Ewa Ellis, Stephen Strom, Mark A Kay, Milton Finegold & Markus Grompe. Robust expansion of human hepatocytes in Fah–/–/Rag2–/–/Il2rg –/– mice. Nature Biotechnology published online 29 July 2007; doi:10.1038/nbt1326.
- World Health Organization (WHO)