Proliferation and differentiation of the small intestinal epithelium: from Petri dish to bedside

The small intestinal epithelium is a continuously renewing cell system in which two main compartments can be defined: the crypt compartment and the villus compartment. The crypt compartment houses the proliferative cells (stem cells) that give birth to the four types of differentiated enterocytes (absorptive enterocytes, goblet cells, enteroendocrine cells, Paneth cells) that, with the exception of Paneth cells, populate the villus compartment. Enterocyte proliferation, differentiation and migration are regulated by a complex network of cell-cell and cell-matrix information, and modulated by growth factors, luminal factors and, possibly, hormones. The intimate mechanisms underlying the fascinating life of the enterocytes are the object of intensive investigation although insights have come from studies "in vitro" and in transgenic animals. The enormous proliferative potential makes the small bowel an extremely plastic organ, able to adapt to various injuries and adverse conditions and to completely recover even from extensive damage. Knowledge of the biologic mechanisms of adaptation has begun to affect therapeutic approaches to a number of intestinal diseases and the future will see a significant advancement in their management. More important, understanding the molecular mechanisms regulating the perfect equilibrium between proliferation and differentiation of the intestinal enterocytes will eventually help disclose the dark side of cancer.