Miniature livers grown from human skin cells were successfully implanted in lab rats and survived for four days inside of their animal hosts, according to a study published today in Cell Reports.
Just like a normal liver, the mini lab-grown made-to-order livers secrete bile acids and urea and reached maturation in less than a month – a process that normally takes place during the first two years of human life.
Researchers at the University of Pittsburgh School of Medicine biofabricated human livers for transplantation in a proof-of-concept experiment, a way of determining whether a method or idea is feasible. Human skin cells (hepatocytes as well as biliary epithelial and vascular endothelial cells) were “reprogrammed” into stem cells, allowing the stem cells to become different types of liver cells. Those cells were then seeded into a rat liver “scaffold” that had all of the rat cells stripped out.
Mini livers were grown in an “organ-like microenvironment” that further matures some liver functions and produces tissue structures similar to those seen in humans before being transplanted into five rats specifically bred to resist organ rejections.
"Seeing that little human organ there inside the animal – brown, looking like a liver – that was pretty cool. This thing that looks like a liver and functions like a liver came from somebody's skin cells," said senior author Alejandro Soto-Gutierrez, MD, PhD, associate professor of pathology at Pitt and faculty member of both the McGowan Institute for Regenerative Medicine and the Pittsburgh Liver Research Center, in a statement.
Rats were shown to have human liver proteins in their blood serum, which suggests a more thorough integration than previously described. While the transplanted mini livers were functional, blood flow issues developed within and around where the organ was grafted.
Though preliminary, the findings could serve as a stepping stone to growing replacement organs in the future and increasing the availability of transplantable livers to treat liver disease. Currently, the only cure for severe liver disease is transplantation, yet there is a high shortage of the organs – in the US alone there are an estimated 17,000 people awaiting a liver transplant, according to Columbia Surgery
"The long-term goal is to create organs that can replace organ donation, but in the near future, I see this as a bridge to transplant," Soto-Gutierrez said. "For instance, in acute liver failure, you might just need [a] hepatic boost for a while instead of a whole new liver."
To effectively graft an engineered organ would require also creating a functioning vascular system that provides essential oxygen and nutrients. Current processes of implanting engineered organs make them highly susceptible to blood clotting, and the authors note that several challenges will need to be overcome in order to make bioengineered organ transplant feasible. The current study focused on short-term survival but notes that further investigation is required to test the liver efficacy. Additionally, the findings were limited due to the small fraction of liver-cell mass used and the vascular complications that occurred after transplantation.
Regardless, the authors note that the strategy they employed “represents a significant advance toward our understanding of the production of bioengineered autologous human-liver grafts for transplantation.”