期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 28, 期 12, 页码 3533-3544出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2016121278
关键词
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资金
- National Institutes of Health [R01 DK 082739]
- Dialysis Clinics Inc. Paul Teschan Research and Development Fund
- IU School of Medicine
- Veterans Affairs Merit Review funds
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 few donor 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 function when 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.
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