Generating liver using blastocyst complementation: Opportunities and challenges

Orthotopic liver transplantation (OLT) is the only definitive treatment option for many patients with end-stage liver disease. Current supply of donor livers for OLT is not keeping up with the growing demand. To overcome this problem, a number of experimental strategies have been developed either to provide a bridge to transplant for patients on the waiting list or to bioengineer whole livers for OLT by replenishing them with fresh supplies of hepatic cells. In recent years, blastocyst complementation has emerged as the most promising approach for generating whole organs and, in combination with gene editing technology, it has revolutionized regenerative medicine. This methodology was successful in producing xenogeneic organs in animal hosts. Blastocyst complementation has the potential to produce whole livers in large animals that could be xenotransplanted in humans, thereby reducing the shortage of livers for OLT. However, significant experimental and ethical barriers remain for the production of human livers in domestic animals, such as the pig. This review summarizes the current knowledge and provides future perspectives for liver xenotransplantation in humans.