Transforming skin cells into liver cells

The Medical College of Wisconsin (MCW) has received a five-year, $2.1 million dollar grant from the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases to advance work pioneered at MCW in which human skin cells are converted into liver cells, and to identify the molecular mechanisms of liver cell development.

Stephen Duncan, D.Phil., the Marcus Professor of Human and Molecular Genetics and director of the MCW Program in Regenerative Medicine and Stem Cell Biology, is the primary investigator of the grant. Dr. Duncan’s faculty appointment is in the department of cell biology, neurobiology and anatomy where the work will be conducted.

More than 30 million Americans have liver disease, and the causes range from genetics, to viruses such as hepatitis C, cancer, nonalcoholic fatty liver disease, and cirrhosis caused by alcoholism.

Dr. Duncan has shown previously that it is possible to produce liver cells, or hiHeps, from human induced pluripotent stem cells that were once simply adult skin cells. Those hiHeps have been used to model infectious liver disease, inborn liver errors, and other liver problems. The procedure appears to closely mirror the development of the liver that occurs during normal growth of the liver in unborn babies.

In this project, Dr. Duncan’s team will use the cell culture model to unravel the complex molecular mechanisms that underlie human liver development—the “why” behind the differentiation and development of a liver.
The experiments are designed to reveal the specific molecular events that occur during that development, which will allow the team to study inborn errors of liver metabolism, and possibly would allow the identification of methods to correct liver diseases.

Ultimately, the project will significantly advance understanding of the molecular basis of liver cell formation, and help realize the full potential of induced adult pluripotent stem cells in the study and treatment of liver disease.

This project is funded by NIH grant R01DK102716-01.