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

16 Citations (Scopus)

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

Fingerprint

Reperfusion Injury
Kidney
Ischemia
Extracellular Vesicles
Exosomes
Multiple Abnormalities
Therapeutics
Neutrophil Infiltration
Wounds and Injuries
Transcriptome
Renal Insufficiency
Fibrosis
Inflammation

ASJC Scopus subject areas

  • Nephrology

Cite this

Renal tubular cell-derived extracellular vesicles accelerate the recovery of established renal ischemia reperfusion injury. / Dominguez, Jesus; Liu, Yunlong; Gao, Hongyu; Dominguez, James M.; Xie, Danhui; Kelly, Katherine.

In: Journal of the American Society of Nephrology, Vol. 28, No. 12, 01.12.2017, p. 3533-3544.

Research output: Contribution to journalArticle

@article{282db167afe54c48a82389bf558abb05,
title = "Renal tubular cell-derived extracellular vesicles accelerate the recovery of established renal ischemia reperfusion injury",
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.",
author = "Jesus Dominguez and Yunlong Liu and Hongyu Gao and Dominguez, {James M.} and Danhui Xie and Katherine Kelly",
year = "2017",
month = "12",
day = "1",
doi = "10.1681/ASN.2016121278",
language = "English (US)",
volume = "28",
pages = "3533--3544",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "12",

}

TY - JOUR

T1 - Renal tubular cell-derived extracellular vesicles accelerate the recovery of established renal ischemia reperfusion injury

AU - Dominguez, Jesus

AU - Liu, Yunlong

AU - Gao, Hongyu

AU - Dominguez, James M.

AU - Xie, Danhui

AU - Kelly, Katherine

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85037074177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037074177&partnerID=8YFLogxK

U2 - 10.1681/ASN.2016121278

DO - 10.1681/ASN.2016121278

M3 - Article

C2 - 28747315

AN - SCOPUS:85037074177

VL - 28

SP - 3533

EP - 3544

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 12

ER -