Injured kidney endothelium is only marginally repopulated by cells of extrarenal origin

Abstract

The role of bone marrow marrow-derived cells after kidney endothelial injury is controversial. In this study, we investigated if and to what extent extrarenal cells incorporate into kidney endothelium after acute as well as during chronic endothelial injury. Fischer F-344 wt (wild type) rat kidney grafts were transplanted into R26- hPAP (human placental alkaline phosphatase) transgenic Fischer F-344 recipient rats to allow identification of extrarenal cells by specific antibody staining. A severe model of renal thrombotic microangiopathy was induced via graft perfusion with antiglomerular endothelial cell (GEN) antibody and resulted in eradication of 85% of the glomerular and 69% of the peritubular endothelium (GEN group). At week 4 after injury, renal endothelial healing as well as recovery of the kidney function was seen. Endothelial chimerism was evaluated by double staining for hPAP and endothelial markers RECA-1 or JG-12. Just 0.25% of the glomerular and 0.1% of the peritubular endothelium was recipient derived. In a second experiment, chronic endothelial injury was induced by combination of kidney transplantation with 5/6 nephrectomy (5/6 Nx group). After 14 wk, only 0.86% of the peritubular and 0.05% of the glomerular endothelium was of recipient origin. In summary, despite demonstration of extensive damage and loss as well as excellent regeneration, just a minority of extrarenal cells were incorporated into kidney endothelium in rat models of acute and chronic renal endothelial cell injury. Our results highlight that kidney endothelial regeneration after specific and severe injury is almost exclusively of renal origin.