Paneth Cells and Lgr5+ Intestinal Stem Cells in Radiation Enteritis

Abstract

Cancer is the leading cause of death in adults and majority of cancers involve abdominal and pelvic organs. Radiotherapy is used in the management of around half of patients who have abdominal and pelvic malignancies and 70% of the treated patients will develop radiation enteritis. The onset of radiation enteritis may delay the completion of treatment or lead to life-threatening conditions such as bowel perforation or obstruction. High-dose ionizing radiation can affect all the layers of the small intestine leading to weakening of its structural integrity, dysbiosis, malabsorption, and derangement of the innate immunity. Advances in the management of cancer has not led to an improvement in the treatment of radiation enteritis as the available preventative or treatment options are still ineffective. Severe acute and chronic radiation enteritis result from the damage to the crypt-based intestinal stem cells and their derivatives, which include the Paneth cells. Paneth cells regulate the proliferation and differentiation of the intestinal stem cells. The other roles of the Paneth cells are protection and nourishment of the intestinal stem cells, and control of the gut microbiota. Paneth cells can also de-differentiate and replace irreversibly damaged intestinal stem cells. This article reviews the anatomy of the epithelium of the small intestine and the intestinal epithelial cells including the Paneth cells. The effect of ionizing radiation on the intestinal stem cells and its derivatives, and the knowledge can be used to develop effective treatment of radiation enteritis is discussed.