Label-retaining cells and tubular regeneration in postischaemic kidney

In this study, we have examined rat kidneys after ischaemic injury (35 min) with regard to the dynamics of S3 tubule regeneration.

One day before ischaemia, each rat received four successive i.p. injections of BrdU (5-bromo-2'-deoxyuridine: 80 mg/kg) at 2 h intervals. Groups of experimental animals (n = 4) were killed every 2 h during the first 24 h post-ischaemia as well as 2, 3, 7 and 14 days post-ischaemia. Renal sections were processed to characterize by immunohistochemistry the distribution and phenotype of BrdU-positive cells.

Renal regeneration after ischaemia was associated with a typical sequence of transient events: (1) absence of immunostaining during the first 8 h after reperfusion; (2) between 8 and 16 h, detection of a small population of BrdU-positive cells (CD44(+), vimentin(+), CD45(-)) restricted to the lumen of blood vessels characterized by the endothelial expression of selectin E; (3) between 16 and 24 h, progressive decrease of labelled cells in renal capillaries and a concomitant increase in the interstitial compartment; (4) after 1 day, labelled cells disappeared progressively from peritubular interstitium and were mainly observed in regenerating S3 tubules, and (5) after 3 days numerous positive cells were only present in regenerated tubules.

Our data suggest that positive cells (BrdU(+), CD44(+), vimentin(+) and CD45(-)) observed in kidney tubules after ischaemia could originate from an extrarenal source and reach the renal parenchyma via blood vessels. We postulate that these immature cells migrate to injured tubules, proliferate and finally differentiate into mature epithelial cells leading to the replacement of a majority (>80%) of altered S3 cells.