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Am J Pathol. 2015 Aug;185(8):2309-23. doi: 10.1016/j.ajpath.2015.04.010. Epub 2015 Jun 12.

Human endothelial colony-forming cells protect against acute kidney injury: role of exosomes.

Author information

1
Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
2
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.
3
Division of Hematology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
4
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.

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.

PMID:
26073035
DOI:
10.1016/j.ajpath.2015.04.010
[Indexed for MEDLINE]

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