Scientists Serve Up a Dish of Pig Liver Cells

Using in vitro techniques, Agricultural Research Service scientists have cultured a pig liver cell line that performs some of the organ's functions in a petri dish.

In swine, humans and other animals, the liver's duties include detoxifying blood, making blood-clotting substances and secreting bile. The pig liver culture, PICM-19, contains hepatocyte and bile duct cells that synthesize serum proteins, show P450 (enzyme) activity and display other liverlike behaviors.

With PICM-19, animal researchers can design in vitro models of the liver to study gene expression, nutrient metabolism, drug toxicity and bile duct formation outside the animal's body, notes Neil Talbot of ARS' Gene Evaluation and Mapping Laboratory in Beltsville, Md.

There, he and Tom Caperna of ARS' Growth Biology Laboratory developed PICM-19 to expedite research aimed at improving swine traits such as lean muscle production. The liver is of interest since it aids digestion and regulates important growth hormones.

In other research, biomedical scientists have used pig liver cells in bio-artificial liver devices (BALD), which are undergoing clinical trials to provide temporary dialysis for human patients. But culturing and maintaining such cells has proven difficult: Once removed from the body, they soon lose their normal functioning.

Starting in 1993, Talbot and Caperna overcame the problem by developing a novel procedure for culturing hepatocyte and bile duct cells from pig embryo stem (ES) cells, as well as from intact pig livers. In a first for swine that may also have biomedical applications, the ARS researchers coaxed the ES cells to become liverlike hepatocytes and bile duct cells, which comprise 98 percent of the organ's tissues.

After four years in continuous culture, PICM-19 has retained its desired properties. Tests with mice show it's not tumor-causing, a feature critical to nutrient metabolism research and BALD applications. PICM-19 also lends itself to developing in vitro alternatives to testing experimental medicines or other substances in live animals, according to Talbot.

ARS, which holds two patents on PICM-19, is the U.S. Department of Agriculture's chief scientific research agency.