Renal tubular cell-derived extracellular vesicles accelerate the recovery of established renal ischemia reperfusion injury

Jesus Dominguez, Yunlong Liu, Hongyu Gao, James M. Dominguez, Danhui Xie, Katherine Kelly

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Ischemic renal injury is a complex syndrome; multiple cellular abnormalities cause accelerating cycles of inflammation, cellular damage, and sustained local ischemia. There is no single therapy that effectively resolves the renal damage after ischemia. However, infusions of normal adult rat renal cells have been a successful therapy in several rat renal failure models. The sustained broad renal benefit achieved by relatively fewdonor cells led to the hypothesis that extracellular vesicles (EV, largely exosomes) derived from these cells are the therapeutic effector in situ. We now show that EV from adult rat renal tubular cells significantly improved renal functionwhen administered intravenously 24 and 48 hours after renal ischemia in rats. Additionally, EV treatment significantly improved renal tubular damage, 4-hydroxynanoneal adduct formation, neutrophil infiltration, fibrosis, and microvascular pruning. EV therapy also markedly reduced the large renal transcriptome drift observed after ischemia. These data show the potential utility of EV to limit severe renal ischemic injury after the occurrence.

Original languageEnglish (US)
Pages (from-to)3533-3544
Number of pages12
JournalJournal of the American Society of Nephrology
Volume28
Issue number12
DOIs
StatePublished - Dec 1 2017

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ASJC Scopus subject areas

  • Nephrology

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