Current treatment for children with Short Bowel Syndrome (SBS) has a 30% 5 year mortality rate and serious morbidities that destroy the quality of life. Surgical and medical therapies are inadequate. Tissue- engineered small intestine (TESI) may offer an alternative and superior means for restoring intestinal length and function. We recently transitioned this model in order to make use of the tools available in the mouse. The long-term goal of this project is a human cure for SBS. TESI will be formed from autologous cells, and after formation, be connected to the shortened intestinal tract to salvage patients. In order to meet regulatory requirements and to increase the chance of success in humans, we must define the necessary and sufficient progenitor cell population by defining the fate of transplanted OU. A knowledge of the serial process of TESI formation from the seeded OU will inform us about cell spreading, time of vascularization, when and how mature mucosa forms, and allow us to manipulate these processes for successful TESI formation in larger animals and humans. In addition, we can expand the crucial progenitor(s) prior to implantation. As another strategy to enhance TESI formation, we are investigating the role of FGF10, a necessary molecule during organogenesis, homeostasis, and injury repair in postnatal life. FGF10 may increase the proliferation of intestinal epithelial progenitor cells, and therefore improve the growth of TESI. We are conducting parallel studies with murine and human tissue, with success with each.