An appraisal of cell loss

The concept of continuous epithelial renewal in the gastrointestinal tract was introduced at the end of the nineteenth century (Patzelt, 1882; Bizzozero, 1888; Schaffer, 1891), and since then labelling experiments with tritium-labelled thymidine have established that epithelial cells are produced in the crypts of the small intestinal mucosa, migrate up onto the villi and are lost at the tips, both in experimental animals (Leblond and Messier, 1958; Quastler and Sherman, 1959; Creamer, Shorter, and Bamforth, 1961) and in man (Shorter, Moertel, Titus, and Reitemeier, 1964; MacDonald, Trier, and Everett, 1964). It has been previously considered that epithelial cells migrate up from the mouth of the crypts directly onto villi on all sides, and it has therefore been assumed that there is an orderly one-to-one relationship of crypts to villi, with one crypt orifice between adjacent villi. In another communication (Loehry and Creamer, 1968) we have established that the crypt-villus relationship in the small intestinal mucosa is more complex than has been assumed, that overall there are many more crypts than villi, that very few of the crypts open out onto villi on all sides, and that, in most cases, much of each crypt opening is adjacent not to villi but to other crypts. The migration therefore of epithelial cells from crypts to villi cannot be a simple direct progression as might be expected from two-dimensional sections. Two possibilities exist: those cells emerging at sites where two crypts are adjacent must either be desquamated here at the crypt mouth or else be channelled round in some way onto villi. Because of this complex crypt-villus relationship it was thought necessary to undertake a reappraisal of cell migration, and, in order to establish whether cells were desquamated at the crypt mouth or channelled onto villi, to study the problem by a consideration of cell loss.