Novel insights into human intestinal epithelial cell proliferation in health and disease using confocal microscopy.

Abstract

Measurement of intestinal epithelial cell proliferation has provided important information concerning tissue responses in neoplasia, enteropathy, and adaptation. This study reexamined current concepts regarding intestinal proliferation by using a novel confocal microscopical technique to map mitotic figures accurately within the intact three dimensional framework of the crypts of Lieberkühn. The ability of confocal microscopy to simultaneously measure crypt morphology and internal detail, without disrupting spatial cell arrangements, has provided important new data. These question the ability of existing methods to accurately measure and interpret proliferative changes in the gut. This work investigates intestinal proliferation in children with coeliac disease, a well defined hyperproliferative disorder, in comparison with the healthy intestine. These results show that crypt cell division occurs with an equal probability in health and disease. In addition, increased crypt cell production rates are largely caused by a change in crypt size rather than a change in cell cycle time or crypt growth fraction and, as such, alter our understanding of kinetic responses in gastrointestinal disease.