The Salk Institute for Biological Sciences is reporting on developing a technique for transplanting human hepatocyte cells into the livers of lab mice, and provide a new way to test treatments for liver disease.
Cells cultured in the lab are like a fish out of water. Often, their behavior does not reflect their biological function within an entire organ or organism, which, for example, turns studying human liver cells into a big challenge.
One way to get around the altered properties of the stranded cells is to populate mouse livers with human hepatocytes in the hope of creating a natural environment, which is exactly what researchers at the Salk Institute for Biological Studies did. They developed a simple system that allows them to transplant human hepatocytes into immunodeficient mice, which can now be used to test how drugs affect the liver…
In fact, that’s the underlying principle of the Salk researchers’ new chimeric mouse. It is based on a murine model for hereditary tyrosinaemia type I, developed by researchers at Oregon Healthy & Science University. An enzymatic defect in the tyrosine catabolism results in a toxic accumulation of byproducts within hepatocytes unless the mice are treated with a drug called NBTC.
Withdrawing the drug allows to selectively expand hepatocytes that do not have this defect, such as transplanted human hepatocytes. Within three months of transplantation, up to 20 percent of the mouse liver is repopulated by human hepatocytes. But what’s more, the transplanted cells keep producing a foreign protein slipped inside with the help of a lentiviral vector, the kind usually used for gene therapy. “We are very excited about that aspect since very often cells shut off the production of proteins introduced as part of gene therapy,” says Verma [Inder Verma, Ph.D., a professor in the Laboratory of Genetics].
Image: Transplanted human liver cells (shown in brown) take hold in the mouse liver and repopulated the host organ over time. The images above show cross sections of mouse liver one month (top), two months (middle), and three months (bottom) after the injection of human hepatocytes.
Courtesy of Dr. Karl-Dimiter Bissig, Salk Institute for Biological Studies
Press release: New chimeric mouse model for human liver diseases, drug testing …
