Endothelial progenitor cells restore renal function in chronic experimental renovascular disease.
BACKGROUND
Endothelial progenitor cells (EPCs) promote neovascularization and endothelial repair. Renal artery stenosis (RAS) may impair renal function by inducing intrarenal microvascular injury and remodeling. We investigated whether replenishment with EPCs would protect the renal microcirculation in chronic experimental renovascular disease.


RESULTS
Single-kidney hemodynamics and function were assessed with the use of multidetector computed tomography in vivo in pigs with RAS, pigs with RAS 4 weeks after intrarenal infusion of autologous EPCs, and controls. Renal microvascular remodeling and angiogenic pathways were investigated ex vivo with the use of micro-computed tomography, histology, and Western blotting. EPCs increased renal expression of angiogenic factors, stimulated proliferation and maturation of new vessels, and attenuated renal microvascular remodeling and fibrosis in RAS. Furthermore, EPCs normalized the blunted renal microvascular and filtration function.


CONCLUSIONS
The present study shows that a single intrarenal infusion of autologous EPCs preserved microvascular architecture and function and decreased microvascular remodeling in experimental chronic RAS. It is likely that restoration of the angiogenic cascade by autologous EPCs 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 EPCs as a promising therapeutic intervention for preserving the kidney in renovascular disease.
Chade
Alejandro R
AR
Division of Nephrology and Hypertension, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Zhu
Xiangyang
X
Lavi
Ronit
R
Krier
James D
JD
Pislaru
Sorin
S
Simari
Robert D
RD
Napoli
Claudio
C
Lerman
Amir
A
Lerman
Lilach O
LO
D000792:Angiography; D000818:Animals; D002908:Chronic Disease; D042783:Endothelial Cells / Q000166:cytology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006977:Hypertension, Renal / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D008833:Microcirculation / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology; D020127:Recovery of Function; D012078:Renal Artery Obstruction / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy*; D012079:Renal Circulation / Q000502:physiology; D034421:Sus scrofa; D014057:Tomography, X-Ray Computed