Summary
Ischaemic necrosis of the villi was produced by occlusion of the superior mesenteric artery for 1 hour and subsequent regeneration of the epithelium examined after 1,2, 4, 8, 16, 24, and 48 hours. Regenerating cells above the crypts were first identified in significant numbers after 2 hours. Complete re-epithelization occasionally seen at 4 hours resulted in mucosa completely devoid of villi. Frequent hyperplastic foci, spurs and synechiae occurred in the sheets of regenerating epithelium at an early stage. Most frequently re-epithelization was complete between 8 and 16 hours and short villi formed which then increased in length. No mitoses were seen. By electron microscopy crypt epithelium showed maximum changes at 2–4 hours. Many crypt cells were affected by coagulation necrosis and included into surviving cells. In addition, there were cytolysomes, which frequently contained only ribosomes. The cells of regenerating epithelium were arranged into one or two, rarely more, layers. A normal arrangement appeared after complete re-epithelization. In early stages, the cell shape was irregular. The basal cells tended to be elongated and sealed the intercellular spaces against the basement membrane by their processes. The basement membrane which showed focal disruption was left after the desquamation of necrotic epithelium. At 4 hours and later, a polar organization of cells was seen. Junctions of the intermediate type were observed after 2 hours. At 4 hours junctional complexes were formed with frequent irregularities in the sequence of their components. The number and regularity of microvilli increased gradually. The first sign of microvillus formation was an elevation of the plasma membrane with condensation of the fuzzy layer; core filaments appeared when the microvillus had reached a certain length. The terminal web was only rudimentary before microvilli were organized to form a brush border. The height of the brush border was less than normal at 24 hours. Interdigitations at the lateral plasma membrane appeared at 16 hours; however, they did not reach normal extent at 24 hours. The first cells in the advancing rows of regenerating epithelium lagged in the surface differentiation until the re-epithelization was completed. The cytoplasm contained numerous free ribosomes and sparse endoplasmic reticulum. The amount of the latter, after 24 hours, was less than normal. A consistent feature of the later stages of regeneration (8–24 hours) was a densification of the mitochondrial matrix and accumulation of lipid droplets within well developed Golgi complexes and within occasional vesicles of endoplasmic reticulum. Cytolysomes developing into residual bodies and inclusions of necrotic cells were frequent in’ the early stages. Nuclei showed prominent nucleoli and occasional clusters of interchromatin granules. The differentiating goblet cells, aside from increased development of endoplasmic reticulum and Golgi complex showed features common to regenerating cells. Degenerative changes affected regenerating cells both on newly forming villi and in aberrant foci.
It is assumed that mitoses in crypts are sufficient to produce cells in the regenerated zone. The early loss of polar organization and simplification of cell surface is interpreted as dedifferentiation. The comparison of sequential stages of regeneration indicates that differentiation takes place with the progress of regeneration. The environmental difference is suggested as a factor. The changes in organelles are similar to regenerating cells in some other tissues and are non-specific though characteristic for rapidly proliferating cells. The degenerative changes which affect some regenerating cells are thought important in reestablishing normal organization.