Evidence map›Paper›PMID 29954220›Full record

ArticleCell transplantation2018

Mesenchymal Stem Cell-Derived Extracellular Vesicles Improve the Renal Microvasculature in Metabolic Renovascular Disease in Swine.

Alfonso Eirin, Xiang-Yang Zhu, Sreela Jonnada, Amir Lerman, Andre J van Wijnen, Lilach O Lerman

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell transplantation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 1 pooled it
9.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

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15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Alfonso Eirin1 Divisions of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Xiang-Yang Zhu1 Divisions of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Sreela Jonnada1 Divisions of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Amir Lerman2 Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
Andre J van Wijnen3 Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
Lilach O Lerman1 Divisions of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Mayo Clinic · USMayo Clinic in Arizona · US

Funding

CT imaging for the assessment of kidney injury distal to renal artery stenosisR01DK073608 · NIDDK · MAYO CLINIC ROCHESTER · PI LERMAN, LILACH O · 2006 to 2015
$3.1M
Ultrasound Shockwave Therapy for Post-Stenotic Microvascular RemodelingR01HL123160 · NHLBI · MAYO CLINIC ROCHESTER · PI LERMAN, AMIR, LERMAN, LILACH O · 2015 to 2018
$3.0M
MSC-derived microvesicles in metabolic syndrome and renovascular diseaseR01DK102325 · NIDDK · MAYO CLINIC ROCHESTER · PI LERMAN, LILACH O · 2015 to 2018
$2.8M
Noninvasive assessment of renal fibrosis using magnetization transfer MRIU01DK104273 · NIDDK · MAYO CLINIC ROCHESTER · PI LERMAN, LILACH O · 2014 to 2018
$1.8M
A potential role for mitoprotection in preserving the kidney in metabolic syndrome and renal artery stenosisK08DK106427 · NIDDK · MAYO CLINIC ROCHESTER · PI EIRIN, ALFONSO · 2015 to 2019
$819k
NHLBI NIH HHS R01 HL123160NIDDK NIH HHS K08 DK106427NIDDK NIH HHS R01 DK073608NIDDK NIH HHS R01 DK102325NIDDK NIH HHS U01 DK104273
6 · The paper itself

Abstract

backgroundExtracellular vesicles (EVs) released from mesenchymal stem/stromal cells (MSCs) mediate their paracrine effect, but their efficacy to protect the microcirculation of the kidney is unknown. Using a novel swine model of unilateral renovascular disease (RVD) complicated by metabolic syndrome (MetS), we tested the hypothesis that EVs would attenuate renal microvascular loss.

methodsFour groups of pigs ( n = 7 each) were studied after 16 weeks of diet-induced MetS and RVD (MetS+RVD), MetS+RVD treated 4 weeks earlier with a single intra-renal delivery of EVs harvested from autologous adipose tissue-derived MSCs, and Lean and MetS Sham controls. Stenotic-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were measured in-vivo (fast CT), whereas EV characteristics, renal microvascular architecture (micro-CT), and injury pathways were studied ex-vivo.

resultsmRNA sequencing and proteomic analysis revealed that EVs are packed with several pro-angiogenic genes and proteins, such as vascular endothelial growth factor. Labeled EVs were detected in the stenotic kidney 4 weeks after injection internalized by tubular and endothelial cells. EVs restored renal expression of angiogenic factors and improved cortical microvascular and peritubular capillary density. Renal apoptosis, oxidative stress, tubular injury, and fibrosis were also attenuated in EV-treated pigs. RBF and GFR decreased in MetS+RVD compared with MetS, but normalized in MetS+RVD+EVs.

conclusionsIntra-renal delivery of MSC-derived EVs bearing pro-angiogenic properties restored the renal microcirculation and in turn hemodynamics and function in chronic experimental MetS+RVD. Our study suggests a novel therapeutic potential for MSC-derived EVs in restoring renal hemodynamics in experimental MetS+RVD.

Indexed as

Renal CirculationAnimalsCells, CulturedExtracellular VesiclesFemaleKidneyKidney DiseasesMesenchymal Stem CellsMetabolic SyndromeMicrovesselsSwineextracellular vesiclesmesenchymal stem cellsmetabolic syndromemicrocirculationrenovascular disease

Identifiers

PMID29954220
PMCPMC6158551
OpenAlexW2811010100

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.