Cellular proliferation in the crypt epithelium of human small intestinal xenografts

The present study investigates the spatial organisation of epithelial cell proliferation in human small intestinal xenografts, in order that direct comparisons can be made with paediatric small bowel. For this purpose we employed the MIB-1 (Ki-67) monoclonal antibody and [3H]thymidine to analyse the crypt growth fraction and DNA synthesising (S-phase) cells, respectively. The spatial distribution of cycling (MIB-1+) cells was appropriately confined to the xenograft crypts where it closely resembled that of paediatric intestine, both in terms of the labelling index and an ability to form runs of labelled cells, thereby demonstrating synchronous patterns of cell division. In addition, the S-phase representation in xenograft intestine was uniform throughout the crypt proliferation compartment thereby indicating cell-cycle homogeneity. This chimeric model system now provides a new approach to investigate altered proliferative responses of human gut to a number of potentially harmful substances e.g. carcinogens, the assessment of which is not feasible in patients or volunteers.