Discussion

This project uses an ex vivo model of radiation-induced, intestinal mucositis. Mouse-derived primary intestinal crypts are grown as “minigut” cultures in complex a 3-dimensional (3D) matrix, without transformation of the cells. These crypts, contain all the cell types present in the small intestinal epithelium, are irradiated and treated with agents to identify substances help to protect the crypts from irradiation. Recombinant proteins, such as keratinocyte growth factor (KGF) and R-Spondin (RSPO1), promote crypt recovery after irradiation, as they do in vivo. Such results support the notion that this ex vivo model reflects the physiology of radiation induced mucositis. Such ex vivo 3D physiological organoid systems represent a bridge between relatively simple in vitro assays using 2D immortalized cell lines and complex in vivo models using whole animals