Lay Teng Ang, PhD

Pilot Research Award
$50,000 over one year

Stanford University

Engineering Mature Hepatocytes from Human Pluripotent Stem Cells for Liver Regeneration

We aim to generate mature human liver cells in the lab for future liver repair therapies. End-stage liver failure is often fatal without transplantation, and many patients do not receive a donor liver in time. We will create a large supply of functional human liver cells in a dish from pluripotent stem cells that can grow indefinitely and can form liver cells. If successful, these cells could one day help support patients with liver failure and help them survive long enough to receive a liver transplant. The key barrier is that stem cell-derived liver cells are immature. Although they harbor many features of liver identity, they do not yet perform the full range of life-sustaining functions carried out by adult liver cells. Mature liver cells break down toxins, process nutrients, produce blood-clotting proteins, and help maintain the body’s metabolism. In contrast, stem cell-derived liver cells show limited functional capacity and may not immediately restore liver function after transplantation into injured livers. This suggests they may need additional maturation to fully support liver repair. We will test whether adult-enriched regulatory factors can mature stem cell-derived liver cells and improve their ability to repair injured liver tissue. We have identified candidate factors highly expressed in adult liver cells, including those that respond to hormones and metabolites in the body. We will introduce these adult factors into stem cell-derived liver cells and determine if they activate mature liver functions. We will then transplant these matured cells into mice with liver injury and test if they engraft better, reduce liver injury, and prolong survival. By defining the regulators that control liver maturation, we could help improve stem cell-derived liver cells for transplantation, disease modeling, and drug testing. More broadly, it could bring us closer to producing reliable, renewable liver cells for patients with life-threatening liver disease.