A liver transplant is currently the only effective treatment for end-stage liver disease. It remains a costly option fraught with risks, not only from the surgical procedure, but also because of lifelong drug therapy to suppress the immune system. McGowan Institute for Regenerative Medicine
faculty member Eric Lagasse, PharmD, PhD (pictured), associate professor in the Department of Pathology at the University of Pittsburgh and the director of the McGowan Institute’s Cancer Stem Cell Center, foresees an alternative to liver transplantation. As recently reported by Michele Baum in PittMed, in Dr. Lagasse’s lab, research efforts focus on the use the body’s lymphatic system to serve as a bioreactor for regenerating a new liver.
“This is the first step of a complex idea that could lead to organogenesis,” says Dr. Lagasse.
In his lab, Dr. Lagasse and his team have found that when you inject liver cells into the peritoneum [the abdominal lining] of a mouse, they migrate to the lymph nodes. “Large nodules then form in the stomach and gut region, and we found out that they were essentially mini-livers,” explains Dr. Lagasse.
Injecting mice with liver cells appears to result in localized migration of hepatocytes to lymph nodes without affecting the function of other, neighboring nodes. In his experiments, in mice with tyrosinemia (a liver defect), transplanted liver cells functioned robustly—enough to rescue the animals from liver failure. The National Institutes of Health thought this approach was so ground-breaking Dr. Lagasse was awarded a 5-year, $2.9 million Director’s Transformative R01 grant in 2009.
“For decades, people have been injecting cells of one kind or another. But it’s an extraordinary leap to think that you can take cells from one organ, inject them into another, and have [those cells] take on the characteristics of the first. Not only that—it works,” says Alan Russell, PhD, director of the McGowan Institute as well as a Pitt University Professor of Surgery with appointments in chemical engineering, bioengineering, and rehabilitation sciences and technology.
A healthy liver removes toxins and waste from the bloodstream and also works to aid digestion and regulate metabolism. There are many kinds of liver disease, yet the most common diagnosis leading to a transplant is cirrhosis, a scarring of the liver often related to long-term alcohol use. Cirrhosis may lead to liver cancer. Liver failure also can be tied to drug interactions, viral infections such as hepatitis C, or chemical poisoning.
Illustration: McGowan Institute for Regenerative Medicine.
PittMed (Spring 2010)
Bio: Dr. Eric Lagasse
Bio: Dr. Alan Russell