Cell tracing studies of endogenous renal repair in a mouse model of reversal of unilateral ureteral obstruction
The mouse model of reversal of unilateral ureteral obstruction (R-UUO) was used to examine the cell type and kidney compartment involved in cell migration and proliferation associated with endogenous renal repair. The structural regenerative response of the kidney following medullary ablation and the pro-fibrotic changes following UUO was examined using the fluorescent dye tracer, CM-DiI.
Male c-fms-EGFP mice underwent UUO for 10 days. At the time of release of UUO, 0.2ul of CM-DiI (10% solution) was injected into different kidney compartments in situ, either within the cortex; the outer medulla; or the papilla. Following two weeks of R-UUO, the pattern of cell migration, proliferation and the cell types that incorporated CM-DiI were determined.
Fluorescence microscopy revealed the cell migratory pattern of CM-DiI labelled cells in 2 week R-UUO kidneys, when cortical repair and restoration of nephron segments in the outer medulla was evident. A clear migration and proliferation of interstitial CM-DiI cells was observed originating from the initial injection site, particularly when CM-DiI was injected into the papilla. FACS analysis demonstrated a significantly higher number of CM-DiI (+) cells in R-UUO kidneys when CM-DiI was injected into the papilla of 10 day UUO mice in situ and followed for 2 weeks of R-UUO.
Ongoing studies are investigating the CM-DiI cells in the renal papilla as a potential cell type that may be important in renal regeneration following injury. These studies highlight a novel approach for investigating the intrinsic renal cells that are involved in endogenous repair processes and cellular replacement.