A team led by Sangeeta Bhatia, a biomedical engineer at the Massachusetts Institute of Technology in Cambridge, made 20-millimetre-long artificial human livers and implanted them into otherwise normal mice. The researchers report today in Proceedings of the National Academy of Sciences that the mice showed metabolism characteristic of the human liver for weeks after implantation.
Although scientists commonly use mice for biomedical research, they are not always helpful for pharmaceutical testing. Because mouse livers react to drugs differently than human livers, they often can't be used to predict whether a potential drug will be toxic to people. That means that a drug that harms the liver could make it all the way to human clinical trials before researchers discover its risks.
"What's exciting to researchers is this idea that if we can create these mice with human livers, we can basically create a slew of human-like patients to do drug-development screens, or to ... develop new therapies," says Alice Chen, an author on the study who works in the lab of Sangeeta Bhatia, the John and Dorothy Wilson Professor of HST and Electrical Engineering and Computer Science.
"The key technique is that we make stable liver implants in the laboratory first," says biomedical engineer Chen The researchers combined human liver cells (hepatocytes) that carry out the liver's metabolic functions, with mouse fibroblast cells and human liver endothelial cells, which provide chemical signals the hepatocytes need to function. They encased the cell packages in a plastic scaffold and implanted them into mice.
When they gave the mice drugs that humans and mice break down differently, the mice produced the same breakdown products (metabolites) and showed the same metabolic interactions between drugs as a human would. The authors hope that the new technology will make drug development safer and less costly, by spotting toxicities before a drug gets to clinical trials.
You can read more of this fascinating story here and here
