In the United States today, approximately one in ten people suffers from liver disease and one in 2,500 children are born with the condition. Liver disease can arise from a number of causes, including genetics, diet, and complications from other diseases and can lead to liver failure, cancer, or death. Liver transplants offer some hope and relief. However, waitlists are long, and many patients succumb before receiving an organ is available.
For many years scientists have marveled both at the liver’s complexity – it performs hundreds of life-sustaining functions – and at its tantalizing capacity for regeneration. In mammals, the liver is the only internal organ with the ability to regrow when damaged or dissected. Naturally, generations of researchers keen on developing more effective treatments for liver disease have sought ways to regenerate liver tissue.
Before regeneration becomes a possibility in the clinic, there are fundamental questions to answer in the lab. Kelly Stevens, PhD, an Assistant Professor of Bioengineering and Lab Medicine and Pathology is a faculty member in the Institute for Stem Cell and Regenerative Medicine (ISCRM). Her lab is harnessing advances in biology and engineering to better understand how the liver works and how to fix it when it doesn’t.
One known factor that inhibits regeneration is scarring – a common result of liver disease. What is less understood, says Stevens, are the forces that underly the relationship between scarring and regeneration. That is the question at the center of the research supported by a recently announced $1 million grant from the W.M. Keck Foundation.
Based in Los Angeles, the W. M. Keck Foundation was established in 1954 by the late W. M. Keck, founder of the Superior Oil Company. The Foundation’s grant making is focused primarily on pioneering efforts in the areas of medical research and science and engineering. The Foundation also supports undergraduate education and maintains a Southern California Grant Program that provides support for the Los Angeles community, with a special emphasis on children and youth.
The grant from the Keck Foundation will fund a three-year effort to shed light on the role of mechanical factors in liver regeneration. Specifically, Stevens and her team will be using a method called Highly Parallel Tissue Grafting to explore the effect of hundreds of customized mechanical microenvironments on human liver regeneration in mice. There are good reasons to use mice. First, previous research has shown that human liver cells are compatible with mouse livers. Second, animal models are more complex than disease-in-a-dish approaches.
“Biologists have tended to focus on the way in which biochemical factors and genes contribute to liver regeneration, mainly because the tools to do this were available and improving,” says Stevens. “The role of mechanical forces in liver regeneration have received much less attention. This is important because when livers become cirrhotic and stiffen, regeneration fails, even though these conditions often progress to cancer, suggesting stiffer environments stimulate proliferation in some conditions.”
It is this paradox that Stevens plans to study with the new grant.
