title: Human endothelial colony-forming cells protect against acute kidney injury: role of exosomes.
abstract: The administration of certain progenitor cells is protective in experimental acute kidney injury (AKI), and mechanisms may involve the release of paracrine factors. Endothelial colony-forming cells (ECFCs) are endothelial precursor cells with a high proliferative capacity and pro-angiogenic potential. We examined the effects of human umbilical cord blood-derived ECFCs and their extracellular vesicles in a mouse model of ischemic AKI and in cultured human umbilical vein endothelial cells subjected to hypoxia/reoxygenation. In mice with ischemic AKI, administration of ECFCs (i.v.) at the time of reperfusion significantly attenuated increases in plasma creatinine, tubular necrosis, macrophage infiltration, oxidative stress, and apoptosis, without cell persistence in the kidneys. In cultured human umbilical vein endothelial cells, hypoxia/reoxygenation stimulated apoptosis. This effect was inhibited by incubation with conditioned medium or exosomes (40- to 100-nm diameter) derived from ECFCs, but not by microparticles (100- to 1000-nm diameter) or vesicle-depleted conditioned medium. Administration of exosomes (i.v.) directly to mice with ischemic AKI attenuated renal injury, as assessed by plasma creatinine, tubular necrosis, and apoptosis. Taken together, these studies indicate protective effects of human cord blood-derived ECFCs in experimental AKI and suggest that ECFC-derived exosomes may mediate the protective response via inhibition of endothelial cell apoptosis.
authors.affiliation: Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Dylan
authors.initials: D
authors.lastname: Burger
authors.affiliation: Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Viñas
authors.affiliation: Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Shareef
authors.initials: S
authors.lastname: Akbari
authors.affiliation: Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Hajira
authors.initials: H
authors.lastname: Dehak
authors.affiliation: Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: William
authors.initials: W
authors.lastname: Knoll
authors.affiliation: Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Gutsol
authors.affiliation: Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Carter
authors.affiliation: Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada; Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
authors.affiliation: Division of Hematology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: David S
authors.initials: DS
authors.lastname: Allan
authors.affiliation: Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: kburns@ottawahospital.on.ca.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Burns
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D055354:Exosomes / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D018919:Neovascularization, Physiologic / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species