Human extracellular microvesicles from renal tubules reverse kidney ischemia-reperfusion injury in rats

PloS One
James M DominguezK J Kelly

Abstract

Hypoxic acute kidney injury, a major unresolved problem, initiates, or aggravates, renal functional and structural decline. There is no treatment for hypoxic acute renal injury and its sequelae. We tested the hypothesis that human kidney tubular cells, or their extracellular vesicles (exosomes), prevent renal injury when infused intravenously 24 hours after 50 minutes of bilateral renal ischemia in Nude rats. Cells and their exosomes were from harvested human kidneys declined for transplantation. Injections of either cells or exosomes, given after 24 and 48 hours of reperfusion, preserved renal function and structure in both treatment groups. However, exosomes were superior to cells; and maintained renal vascular and epithelial networks, prevented renal oxidant stress, and apoptosis; and restrained activation of pro-inflammatory and pro-fibrogenic pathways. Exosomes worked in 24 hours, consistent with functional rather than regenerative activity. Comprehensive proteomic analysis identified 6152 renal proteins from all cellular compartments; and 628 were altered by ischemia at all cell levels, while 377 were significantly improved by exosome infusions. We conclude that renal damage from severe ischemia was broad, and human renal...Continue Reading

References

Apr 25, 1997·The Journal of Biological Chemistry·C W PughP J Ratcliffe
Jun 1, 1997·British Journal of Urology·C F IslamP A Grace
Dec 26, 2001·Current Opinion in Nephrology and Hypertension·Joseph V Bonventre
May 9, 2002·American Journal of Physiology. Renal Physiology·Sergey V BrodskyMichael S Goligorsky
Apr 5, 2003·American Journal of Physiology. Cell Physiology·K J KellyPierre C Dagher
Feb 1, 2005·The American Journal of Pathology·Benedetta BussolatiGiovanni Camussi
Sep 24, 2005·Journal of the American Society of Nephrology : JASN·Glenn M ChertowDavid W Bates
Jul 19, 2008·American Journal of Nephrology·Samuel N HeymanChristian Rosenberger
Mar 27, 2009·American Journal of Physiology. Renal Physiology·Katherine J KellyJesus H Dominguez
Aug 7, 2009·American Journal of Physiology. Renal Physiology·K J KellyJesus H Dominguez
Jun 11, 2010·American Journal of Physiology. Renal Physiology·Katherine J KellyJesus H Dominguez
Dec 3, 2010·American Journal of Physiology. Renal Physiology·David P BasileTimothy A Sutton
May 18, 2012·American Journal of Physiology. Renal Physiology·Katherine J KellyJesus H Dominguez
Oct 23, 2012·Journal of the American Society of Nephrology : JASN·Christodoulos XinarisGiuseppe Remuzzi
Oct 9, 2014·Annual Review of Physiology·Stella Kourembanas
Oct 29, 2014·American Journal of Physiology. Renal Physiology·Shinji TanakaMasaomi Nangaku
Feb 11, 2015·American Journal of Nephrology·Katherine J KellyJesus H Dominguez
Apr 23, 2015·Journal of the American Society of Nephrology : JASN·Federica CollinoGiovanni Camussi
Sep 16, 2015·Journal of the American Society of Nephrology : JASN·Peter P ReeseScott D Halpern
Jan 16, 2016·Annual Review of Medicine·Anna Zuk, Joseph V Bonventre
Feb 11, 2016·Journal of the American Society of Nephrology : JASN·Anupam AgarwalUNKNOWN Acute Dialysis Quality Initiative XIII Working Group
Mar 29, 2016·Journal of Cellular Physiology·Erik H KoritzinskyPeter S T Yuen
Nov 2, 2016·Journal of the American Society of Nephrology : JASN·Wilna OosthuyzenJames W Dear
Aug 17, 2016·Human Immunology·Connie J WangAjay K Israni
Jul 28, 2017·Journal of the American Society of Nephrology : JASN·Jesus H DominguezK J Kelly

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Citations

Dec 27, 2018·Journal of Cellular and Molecular Medicine·Lin-Li LvBi-Cheng Liu
Apr 18, 2019·Molecular and Cellular Biochemistry·Alyssa CobbsXueying Zhao
Sep 19, 2020·Journal of Extracellular Vesicles·Kristen PopowskiKe Cheng
Feb 23, 2020·Frontiers in Pharmacology·Visith Thongboonkerd
Jul 12, 2020·Journal of Nephrology·J T KurzhagenH Rabb
Jan 5, 2020·Stem Cell Research & Therapy·Chao LiuXuefeng Sun
Jul 1, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Mojahid AliSi Pham
Nov 24, 2020·Hypertension·Olga Martinez-ArroyoRaquel Cortes
Dec 19, 2020·Intensive Care Medicine Experimental·Felix BehrensSzandor Simmons
Apr 2, 2021·Stem Cell Research & Therapy·Yuling Huang, Lina Yang
May 3, 2021·Free Radical Biology & Medicine·Diana Karpman, Ashmita Tontanahal
Apr 20, 2021·Kidney Research and Clinical Practice·Sul A LeeTae-Hyun Yoo
Jun 30, 2021·Trends in Molecular Medicine·Lilach O Lerman
May 30, 2021·Tissue Engineering and Regenerative Medicine·Dong Jun Park, Young Joon Seo

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Methods Mentioned

BETA
electron microscopy
PCR

Software Mentioned

SALINE

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