Proliferative and morphological adaptation of the intestine to experimental resection.

The proliferative and morphological adaptation of the residual intestine following resection is briefly reviewed. Within days after a partial intestinal resection, the number of crypt cells increases. There is a proportional increase in the number of proliferative cells, thus there is no change in the growth fraction. Villus height and morphological complexity increases, particularly in the ileum. The thickness of the muscularis mucosae increases, most likely through an increase in cellularity. The size of the adaptive response is dependent on the amount of tissue removed. The possibility of an adaptive change in the number and proliferative characteristics of rat intestinal stem cells was investigated using the microcolony assay (38). Regenerative foci of mucosal epithelium were quantitated as a function of 137Cs gamma ray irradiation in control or 30 days after a 60% resection of the combined jejunum and ileum. Hydroxyurea, (HU), an S phase cytotoxic agent was given to one group of control and one group of resected rats five minutes before a single dose of radiation. HU had little effect on control jejunum or ileum, however, HU reduced the clonogenic cell survival by over tenfold in resected animals which implies a post-resection change in the intestinal stem cell age distribution. The radiation dose-survival curve of clonogenic cells was shifted to the right after resection compared to control values. These results suggest that an increase in intestinal stem cell number and a shift in the proliferative characteristics (from slowly to rapidly cycling) occur as an adaptive response to intestinal resection.