Immunostaining of human pluripotent stem cell (hPSCs) derived hepatic aggregates, showing co expression of Albumin (red) and ASGR1 (hepatocyte specific glycoprotein) (green) and the nuclei by DAPI (blue). (Image provided by Ogawa lab).
Gordon Keller, director of the McEwen Stem Cell Institute, University Health Network (UHN), leads a team of eight labs focused on developing new stem cell-based therapies to treat liver disease .
The team is working on projects that aim to develop a complete molecular map of the liver, to generate liver cells from stem cells and to engineer functional liver tissue with these cells.
“For patients who are struggling with end-stage liver disease and have no transplant option, the restoration of liver function through the transplantation of stem cell-derived liver cells would have a life-changing impact,” says Keller.
Beginning with a pluripotent stem cell — which can transform into almost any human cell — the lab of Shinichiro Ogawa, (affiliate scientist, McEwen Stem Cell Institute), has established a method to make different types of liver cells in a culture dish. The long-term goal is to transplant these lab-grown liver cells into a patient’s liver to regenerate healthy tissue and restore normal organ function.
Gordon Keller, director of the McEwen Stem Cell Institute at the University Health Network.
The Keller lab has made progress in the treatment of hemophilia A, a disease caused by a missing or defective “factor VIII,” a blood-clotting protein that is synthesized by a specific type of blood vessel cell in the liver. The Keller team succeeded in producing these blood vessel cells from stem cells and showed that following transplantation into animal models of Hemophilia A, these cells would grow in the liver, produce functional factor VIII and reduce the severity of the disease.
But the team’s lab work extends beyond cell therapy to treat disease. The liver cells are also being used to engineer liver tissue with the different cell types found in the adult liver: the functional cells known as hepatocytes; the cells that make up the bile duct known as cholangiocytes; the blood vessel cells; and cells of the immune system. The goal is to engineer sufficient functional liver tissue to transplant into a patient with liver failure.
Keller is a stem cell pioneer who played a role in the launch of BlueRock Therapeutics, a leading engineered cell therapy company, which was acquired by Bayer AG.
Back to “Five ways Medicine by Design is transforming the treatment of liver disease.”
