Endothelial progenitor cells restore renal function in chronic experimental renovascular disease

Background—Endothelial progenitor cells (EPC) promote neovascularization and endothelial repair. Renal artery stenosis (RAS) may impair renal function by inducing intra-renal microvascular (MV) injury and remodeling. We investigated whether replenishment with EPC would protect the renal microcirculation in chronic experimental renovascular disease. Methods and results—Single-kidney hemodynamics and function were assessed using multidetector CT in-vivo in pigs with RAS, RAS 4 weeks after intra-renal infusion of autologous EPC, and controls. Renal MV remodeling and angiogenic pathways were investigated ex-vivo using micro- CT, histology, and Western-blotting. EPC increased renal expression of angiogenic factors, stimulated proliferation and maturation of new vessels, and attenuated renal MV remodeling and fibrosis in RAS. Furthermore, EPC normalized the blunted renal MV and filtration function. Conclusions—The current study shows that a single intra-renal infusion of autologous EPC preserved MV architecture and function and decreased MV remodeling in experimental chronic RAS. Likely, restoration of the angiogenic cascade by autologous EPC involved not only generation of new vessels, but also acceleration of their maturation and stabilization. This contributed to preserving the blood supply, hemodynamics, and function of the RAS kidney, supporting EPC as a promising therapeutic intervention for preserving the kidney in renovascular disease.