Theoretical implications for cell migration through the crypt and the villus of labelling studies conducted at each...

The migration and turnover of epithelial cells was examined in the crypt and villus of the mouse jejunum using 1-micron plastic and 6-microns paraffin sections both with or without [3H]thymidine radioautography. The mean diameter of columnar cells was constant at 13.8 microns throughout the crypt, whereas it gradually increased from 16.8 microns in the lower villus to 25.4 microns in the upper villus. The cell cycle time (Tc) and the duration of DNA synthesis (ts) obtained by plotting labelled mitoses against time after [3H]thymidine injection, were 13.4 and 7.5 hr respectively. The labelling index (LI) at the various cell positions in the crypt, of mean length 27.5 cells, averaged 28.6% with a peak of above 55% in positions 7 to 11. The migration velocity of cells in the villus epithelium was estimated from the leading labelled cells at 2.04 cell/hr. The fraction of epithelial cells present in crypt and villus was 0.44 and 0.56 respectively. The migration velocity in the crypt (expressed as cell positions entered per hour), calculated from a cumulative cell production rate (LI/ts) in each cell position, increased in the lower and middle crypt (that is, in the proliferative zone, cell positions 1-18), but remains constant at a level of 1.0 in the upper crypt in the non-proliferative zone (cell positions 19-28). Therefore the migration velocity increases from 1.05 cell/hr in the upper crypt to 2.04 at the base of villus. Accordingly the velocity (expressed as distance traversed per hour) also shifts from 13.8 microns in the upper crypt to 34.2 microns in the base of villus and further increases to 51.8 microns in the upper villus because of continuous enlargement of the cells. The transit times of epithelial cells through the non-proliferative upper crypt (above ten cell positions) and the villus (67.9 cell positions on the average) are 8.4 and 33.4 hr respectively. The turnover times of crypt, villus, and whole epithelium are estimated at 26.5, 33.4, and 59.6 hr respectively.