Project Summary: Currently, there is a need for strategies that mitigate acute radiation-induced gastrointestinal syndrome (RIGS). The risk of large populations including children encountering radiation exposure is real and growing. Although some studies have been performed in development of MCM targeting adult population almost no information is available for pediatric population. Unavailability of a suitable pediatric models further limits any progress on development of MCM for children. The high radiosensitivity of the intestinal epithelium increases susceptibility to RIGS; and with mortality within 10-15 days there is limited time for therapeutic intervention. We have developed a human myeloid committed progenitor (MCP) cell therapy which can mitigate RIGS and improve survival when applied 24 hr after an otherwise lethal dose of radiation exposure. These progenitor cells are modulated ex-vivo to increase expression of WNT ligand, a major paracrine signal for intestinal epithelial regeneration. In this project we will fully characterize RIGS using pediatric rodent model. Finally we will evaluate the involvement of MCP derived WNT signaling in repair and regeneration of intestinal stem cells in this model.