title: Extrarenal Progenitor Cells Do Not Contribute to Renal Endothelial Repair.
abstract: Endothelial progenitor cells (EPCs) may be relevant contributors to endothelial cell (EC) repair in various organ systems. In this study, we investigated the potential role of EPCs in renal EC repair. We analyzed the major EPC subtypes in murine kidneys, blood, and spleens after induction of selective EC injury using the concanavalin A/anti-concanavalin A model and after ischemia/reperfusion (I/R) injury as well as the potential of extrarenal cells to substitute for injured local EC. Bone marrow transplantation (BMTx), kidney transplantation, or a combination of both were performed before EC injury to allow distinction of extrarenal or BM-derived cells from intrinsic renal cells. During endothelial regeneration, cells expressing markers of endothelial colony-forming cells (ECFCs) were the most abundant EPC subtype in kidneys, but were not detected in blood or spleen. Few cells expressing markers of EC colony-forming units (EC-CFUs) were detected. In BM chimeric mice (C57BL/6 with tandem dimer Tomato-positive [tdT+] BM cells), circulating and splenic EC-CFUs were BM-derived (tdT+), whereas cells positive for ECFC markers in kidneys were not. Indeed, most BM-derived tdT+ cells in injured kidneys were inflammatory cells. Kidneys from C57BL/6 donors transplanted into tdT+ recipients with or without prior BMTx from C57BL/6 mice were negative for BM-derived or extrarenal ECFCs. Overall, extrarenal cells did not substitute for any intrinsic ECs. These results demonstrate that endothelial repair in mouse kidneys with acute endothelial lesions depends exclusively on local mechanisms.
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Jan
authors.initials: J
authors.lastname: Sradnick
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Song
authors.initials: S
authors.lastname: Rong
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Anika
authors.initials: A
authors.lastname: Luedemann
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Parmentier
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bartaun
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Vladimir T
authors.initials: VT
authors.lastname: Todorov
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Faikah
authors.initials: F
authors.lastname: Gueler
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hugo
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; and bernd.hohenstein@uniklinikum-dresden.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Hohenstein
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D042783:Endothelial Cells / Q000502:physiology*; D004727:Endothelium / Q000502:physiology; D007668:Kidney / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013234:Stem Cells / Q000502:physiology*
keywords: endothelial injury; endothelial progenitor cell; endothelial repair; glomerulonephritis; thrombotic