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Abstract: PO0881

Renal Endothelial Cells After Injury Were Dominantly Regenerated by an Adult Renal Endothelial Cell Pool

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Sradnick, Jan, Division of Nephrology, Department of Internal Medicine III, University Hospital CGC, Dresden, Saxony, Germany
  • Bunk, Nicole, Division of Nephrology, Department of Internal Medicine III, University Hospital CGC, Dresden, Saxony, Germany
  • Wirth, Anika, Division of Nephrology, Department of Internal Medicine III, University Hospital CGC, Dresden, Saxony, Germany
  • Todorov, Vladimir T., Division of Nephrology, Department of Internal Medicine III, University Hospital CGC, Dresden, Saxony, Germany
  • Hugo, Christian, Division of Nephrology, Department of Internal Medicine III, University Hospital CGC, Dresden, Saxony, Germany
Background

Previously we demonstrated that endothelial repair in murine kidneys exclusively depends on local renal mechanisms. This is related to the question whether a renal non-endothelial (precursor) cell pool/niche exists parallel to local endothelial cell proliferation.

Methods

Inducible Cdh5(PAC)-ERT2 tdTomato (tdT) reporter mice were used to assess the proportion of renal endothelial cells regenerating exclusively from labelled endothelial cells, which persisted after selective endothelial cell injury (ECI) in individualized animals. ECI was induced by renal arterial perfusion of the left kidney with ConcanavalinA (ConA)/anti-ConA. The recombination efficiency of tamoxifen-induced mice was determined 24h prior to ECI by flow cytometric analysis. 24h after ECI, a biopsy of the previously damaged kidney was taken to determine the degree of endothelial damage. One week after ECI the mice were sacrificed and all kidneys were examined by flow cytometry (CD105+CD31+CD45-) and histology (CD31+ERG+ cell/glomeruli). Sham operated mice (SHAM) and the intact contralateral kidney (CL) served as controls.

Results

More than 85% of all renal endothelial cells expressed tdT in 19 of 27 induced mice, which were selected for further experiments. The mean labelling efficiency with tdT was 94.1% of all endothelial cells. Seven mice served as sham. 24h after ECI (n=12), and a 28.6±9% reduction of glomerular ERG+ endothelial cells (8.7±1.1 cells) vs. sham control mice (13.5±0.9 cells) was observed (p<0.02). Seven days after ECI, the number of ERG+ glomerular cells was not significantly different compared to the non-damaged kidney or sham (d7 ECI:12.4±1.9 cells vs CL:13.1±0.8 cells; SHAM:13.5±0.9 cells) demonstrating complete repair. Hereby, the proportion of tdT positive cells did not significantly differ between any of the groups, neither at different time points (24h: 92.8%; d7 ECI: 91.2%) nor between sham and injured kidneys one week following ECI (ECI: 91.2%; CL: 93.6%; SHAM 94.2%).

Conclusion

In individualized inducible Cdh5(PAC)-ERT2 tdT reporter mice, the percentage of tdTomato positive versus total endothelial cells does not change during/after endothelial regeneration. This experimental study suggests that the renal endothelium regenerates from an existing intrarenal endothelial cell pool and not from a non-endothelial precursor cell pool.