Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation

Alfonso Eirin, Xiang Yang Zhu, Amrutesh S. Puranik, Hui Tang, Kelly A. McGurren, Andre J van Wijnen, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Mesenchymal stem/stromal cells (MSCs) have distinct capability for renal repair, but may have safety concerns. MSC-derived extracellular vesicles emerged as a novel noncellular alternative. Using a porcine model of metabolic syndrome and renal artery stenosis we tested whether extracellular vesicles attenuate renal inflammation, and if this capacity is mediated by their cargo of the anti-inflammatory cytokine interleukin (IL) 10. Pigs with metabolic syndrome were studied after 16 weeks of renal artery stenosis untreated or treated four weeks earlier with a single intrarenal delivery of extracellular vesicles harvested from adipose tissue-derived autologous MSCs. Lean and sham metabolic syndrome animals served as controls (seven each). Five additional pigs with metabolic syndrome and renal artery stenosis received extracellular vesicles with pre-silenced IL10 (IL10 knock-down). Single-kidney renal blood flow, glomerular filtration rate, and oxygenation were studied in vivo and renal injury pathways ex vivo. Retention of extracellular vesicles in the stenotic kidney peaked two days after delivery and decreased thereafter. Four weeks after injection, extracellular vesicle fragments colocalized with stenotic-kidney tubular cells and macrophages, indicating internalization or fusion. Extracellular vesicle delivery attenuated renal inflammation, and improved medullary oxygenation and fibrosis. Renal blood flow and glomerular filtration rate fell in metabolic syndrome and renal artery stenosis compared to metabolic syndrome, but was restored in pigs treated with extracellular vesicles. These renoprotective effects were blunted in pigs treated with IL10-depleted extracellular vesicles. Thus, extracellular vesicle-based regenerative strategies might be useful for patients with metabolic syndrome and renal artery stenosis.

Original languageEnglish (US)
JournalKidney International
DOIs
StateAccepted/In press - May 24 2016

Fingerprint

Mesenchymal Stromal Cells
Inflammation
Kidney
Renal Artery Obstruction
Swine
Interleukin-10
Renal Circulation
Glomerular Filtration Rate
Extracellular Vesicles
Adipose Tissue
Fibrosis
Anti-Inflammatory Agents
Macrophages
Cytokines
Safety
Injections
Wounds and Injuries

Keywords

  • Extracellular vesicles
  • Interleukin-10
  • Mesenchymal stem cells
  • Metabolic syndrome
  • Renal artery stenosis

ASJC Scopus subject areas

  • Medicine(all)
  • Nephrology

Cite this

Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation. / Eirin, Alfonso; Zhu, Xiang Yang; Puranik, Amrutesh S.; Tang, Hui; McGurren, Kelly A.; van Wijnen, Andre J; Lerman, Amir; Lerman, Lilach O.

In: Kidney International, 24.05.2016.

Research output: Contribution to journalArticle

Eirin, Alfonso ; Zhu, Xiang Yang ; Puranik, Amrutesh S. ; Tang, Hui ; McGurren, Kelly A. ; van Wijnen, Andre J ; Lerman, Amir ; Lerman, Lilach O. / Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation. In: Kidney International. 2016.
@article{503f7d9c58ff43f9b5612c7203318e2f,
title = "Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation",
abstract = "Mesenchymal stem/stromal cells (MSCs) have distinct capability for renal repair, but may have safety concerns. MSC-derived extracellular vesicles emerged as a novel noncellular alternative. Using a porcine model of metabolic syndrome and renal artery stenosis we tested whether extracellular vesicles attenuate renal inflammation, and if this capacity is mediated by their cargo of the anti-inflammatory cytokine interleukin (IL) 10. Pigs with metabolic syndrome were studied after 16 weeks of renal artery stenosis untreated or treated four weeks earlier with a single intrarenal delivery of extracellular vesicles harvested from adipose tissue-derived autologous MSCs. Lean and sham metabolic syndrome animals served as controls (seven each). Five additional pigs with metabolic syndrome and renal artery stenosis received extracellular vesicles with pre-silenced IL10 (IL10 knock-down). Single-kidney renal blood flow, glomerular filtration rate, and oxygenation were studied in vivo and renal injury pathways ex vivo. Retention of extracellular vesicles in the stenotic kidney peaked two days after delivery and decreased thereafter. Four weeks after injection, extracellular vesicle fragments colocalized with stenotic-kidney tubular cells and macrophages, indicating internalization or fusion. Extracellular vesicle delivery attenuated renal inflammation, and improved medullary oxygenation and fibrosis. Renal blood flow and glomerular filtration rate fell in metabolic syndrome and renal artery stenosis compared to metabolic syndrome, but was restored in pigs treated with extracellular vesicles. These renoprotective effects were blunted in pigs treated with IL10-depleted extracellular vesicles. Thus, extracellular vesicle-based regenerative strategies might be useful for patients with metabolic syndrome and renal artery stenosis.",
keywords = "Extracellular vesicles, Interleukin-10, Mesenchymal stem cells, Metabolic syndrome, Renal artery stenosis",
author = "Alfonso Eirin and Zhu, {Xiang Yang} and Puranik, {Amrutesh S.} and Hui Tang and McGurren, {Kelly A.} and {van Wijnen}, {Andre J} and Amir Lerman and Lerman, {Lilach O}",
year = "2016",
month = "5",
day = "24",
doi = "10.1016/j.kint.2016.12.023",
language = "English (US)",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation

AU - Eirin, Alfonso

AU - Zhu, Xiang Yang

AU - Puranik, Amrutesh S.

AU - Tang, Hui

AU - McGurren, Kelly A.

AU - van Wijnen, Andre J

AU - Lerman, Amir

AU - Lerman, Lilach O

PY - 2016/5/24

Y1 - 2016/5/24

N2 - Mesenchymal stem/stromal cells (MSCs) have distinct capability for renal repair, but may have safety concerns. MSC-derived extracellular vesicles emerged as a novel noncellular alternative. Using a porcine model of metabolic syndrome and renal artery stenosis we tested whether extracellular vesicles attenuate renal inflammation, and if this capacity is mediated by their cargo of the anti-inflammatory cytokine interleukin (IL) 10. Pigs with metabolic syndrome were studied after 16 weeks of renal artery stenosis untreated or treated four weeks earlier with a single intrarenal delivery of extracellular vesicles harvested from adipose tissue-derived autologous MSCs. Lean and sham metabolic syndrome animals served as controls (seven each). Five additional pigs with metabolic syndrome and renal artery stenosis received extracellular vesicles with pre-silenced IL10 (IL10 knock-down). Single-kidney renal blood flow, glomerular filtration rate, and oxygenation were studied in vivo and renal injury pathways ex vivo. Retention of extracellular vesicles in the stenotic kidney peaked two days after delivery and decreased thereafter. Four weeks after injection, extracellular vesicle fragments colocalized with stenotic-kidney tubular cells and macrophages, indicating internalization or fusion. Extracellular vesicle delivery attenuated renal inflammation, and improved medullary oxygenation and fibrosis. Renal blood flow and glomerular filtration rate fell in metabolic syndrome and renal artery stenosis compared to metabolic syndrome, but was restored in pigs treated with extracellular vesicles. These renoprotective effects were blunted in pigs treated with IL10-depleted extracellular vesicles. Thus, extracellular vesicle-based regenerative strategies might be useful for patients with metabolic syndrome and renal artery stenosis.

AB - Mesenchymal stem/stromal cells (MSCs) have distinct capability for renal repair, but may have safety concerns. MSC-derived extracellular vesicles emerged as a novel noncellular alternative. Using a porcine model of metabolic syndrome and renal artery stenosis we tested whether extracellular vesicles attenuate renal inflammation, and if this capacity is mediated by their cargo of the anti-inflammatory cytokine interleukin (IL) 10. Pigs with metabolic syndrome were studied after 16 weeks of renal artery stenosis untreated or treated four weeks earlier with a single intrarenal delivery of extracellular vesicles harvested from adipose tissue-derived autologous MSCs. Lean and sham metabolic syndrome animals served as controls (seven each). Five additional pigs with metabolic syndrome and renal artery stenosis received extracellular vesicles with pre-silenced IL10 (IL10 knock-down). Single-kidney renal blood flow, glomerular filtration rate, and oxygenation were studied in vivo and renal injury pathways ex vivo. Retention of extracellular vesicles in the stenotic kidney peaked two days after delivery and decreased thereafter. Four weeks after injection, extracellular vesicle fragments colocalized with stenotic-kidney tubular cells and macrophages, indicating internalization or fusion. Extracellular vesicle delivery attenuated renal inflammation, and improved medullary oxygenation and fibrosis. Renal blood flow and glomerular filtration rate fell in metabolic syndrome and renal artery stenosis compared to metabolic syndrome, but was restored in pigs treated with extracellular vesicles. These renoprotective effects were blunted in pigs treated with IL10-depleted extracellular vesicles. Thus, extracellular vesicle-based regenerative strategies might be useful for patients with metabolic syndrome and renal artery stenosis.

KW - Extracellular vesicles

KW - Interleukin-10

KW - Mesenchymal stem cells

KW - Metabolic syndrome

KW - Renal artery stenosis

UR - http://www.scopus.com/inward/record.url?scp=85013646107&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85013646107&partnerID=8YFLogxK

U2 - 10.1016/j.kint.2016.12.023

DO - 10.1016/j.kint.2016.12.023

M3 - Article

C2 - 28242034

AN - SCOPUS:85013646107

JO - Kidney International

JF - Kidney International

SN - 0085-2538

ER -