Grant: Project Grant

Over 100 liver diseases collectively impact 1 in 4 Canadians, and this costly burden grows yearly. In many liver diseases, the endothelial cells that form the inner lining of blood vessels lose special functions needed to sustain the organ's 500+ life supporting tasks. Unfortunately, little is known about what keeps liver endothelium working properly. This proposal will leverage pluripotent stem cells, which can become any of the body's cells, to make liver endothelium and study how these cells gain and keep their unique functions. This work will equitably train diverse and highly skilled Canadians as "Cell Therapists" to guide damaged liver endothelium back to health with new therapies or replace damaged cells completely, revitalizing the liver. In the proposed work, we will guide these pluripotent stem cells to become special endothelial cells which, once injected into mice, can live, grow, and mature in the liver. Within the liver, these cells become fully functional liver endothelium that, with careful characterization, will teach us how this maturation process occurs. The proposed studies will build a map of how each function of the liver endothelial cells develops and the order of signals that impart each function. This knowledge will give new treatments and hope for patients with acute and chronic liver diseases as well as liver cancer and Hemophilia A. With life and health span improvements for patients, Canada will benefit from reduced healthcare costs and socioeconomic burdens as the proposed cell-informed and cell-based therapies mobilize private sector partners and move into the clinic.