Functional characterization of late outgrowth endothelial progenitor cells in patients with end-stage renal failure.
Renal transplantation is potentially curative in renal failure, but long-term efficacy is limited by untreatable chronic rejection. Endothelial damage contributes to chronic rejection and is potentially repairable by circulating endothelial progenitor cells (EPC). The frequency and function of EPC are variably influenced by end-stage renal failure (ESRF). Here, we isolated and functionally characterized the late outgrowth EPC (LO-EPC) from ESRF patients to investigate their potential for endothelial repair. Patients with ESRF generated more LO-EPC colonies than healthy controls and had higher plasma levels of IL-1rα, IL-16, IL-6, MIF, VEGF, Prolactin, and PLGF. Patients' LO-EPC displayed normal endothelial cell morphology, increased secretion of PLGF, MCP-1, and IL-1β, and normal network formation in vitro and in vivo. They demonstrated decreased adhesion to extracellular matrix. Integrin gene profiles and protein expression were comparable in patients and healthy volunteers. In some patients, mesenchymal stem cells (MSC) were co-isolated and could be differentiated into adipocytes and osteocytes in vitro. This is the first study to characterize LO-EPC from patients with ESRF. Their behavior in vitro reflects the presence of elevated trophic factors; their ability to proliferate in vitro and angiogenic function makes them candidates for prevention of chronic rejection. Their impaired adhesion and the presence of MSC are areas for potential therapeutic intervention.
Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Jing
J
Zhao
Eleanor M
EM
Bolton
Lucy
L
Randle
John Andrew
JA
Bradley
Andrew M L
AM
Lever
D000328:Adult; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D006801:Humans; D016023:Integrins / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000473:pathology*; D008297:Male; D018919:Neovascularization, Physiologic
D016207:Cytokines; D016023:Integrins
chronic rejection; end-stage renal failure; endothelial progenitor cells; integrin; mesenchymal stem cells; renal transplantation