Immunosuppressive effect of mesenchymal stem cell-derived exosomes on a concanavalin A-induced liver injury modelReport as inadecuate




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Inflammation and Regeneration

, 36:26

First Online: 17 November 2016Received: 24 August 2016Accepted: 01 November 2016

Abstract

BackgroundThis study aimed to evaluate the effect of mesenchymal stem cell MSC-derived exosomes on an immune-induced liver injury model. MSCs show a unique function to modulate immune reaction although the molecular mechanisms are still under investigation. Exosomes are a nanoparticle containing microRNA and many ligands and are recognized as important factors secreted from MSC to express their function. This research is undertaken to evaluate the effect of MSC-derived exosome on concanavalin-A con-A-induced liver injury.

MethodsExosomes were collected from the supernatant of MSC from the bone marrow of C57B6 mice with ultracentrifugation. The collected exosomes or MSCs were injected intravenously into liver injury mice that had been prepared by the intravenous con-A injection. Liver and serum samples were collected 24 h later to evaluate the macro- and microscopic images, the alanine aminotransferase ALT, and cytokine messenger RNA mRNA expression levels. Phenotypical change of non-parenchymal liver cells was also evaluated by flow cytometry. Liver localization of PKH26 after the injection of PKH26-labeled exosomes or MSCs was observed by microscope. Each result was statistically analyzed with Student’s t test.

ResultsPKH was observed in the liver after PKH-labeled exosomes were injected into mouse, whereas it was only observed in the lung in a mouse group receiving PKH-leveled MSC. There were decreases in ALT, liver necrotic areas, and the extent of apoptosis indicated by the single-stranded DNA index of groups that received multiple injections of MSC-derived exosomes, but an increase in the Ki-67 index. The mRNA expression of anti-inflammatory cytokines was enhanced. The number of Treg was increased among NPCs in a group receiving exosomes multiple times.

ConclusionsSuppression of con-A-induced liver injury by injection of exosomes was observed as same extent as MSC. Considering the advantage of exosomes as its non-living nature and dosing adjustability over MSC, exosome will be one alternative of MSC transplantation.

KeywordsExosome Mesenchymal stem cell Concavanalin-A Immune-induced liver injury Nanovesicle Transplantation AbbreviationsALTAlanine aminotransferase

con-AConcanavalin-A

DMEMDulbecco’s modified Eagle’s medium

FBSFetal bovine serum

GAPDHGlyceraldehyde-3-phosphate dehydrogenase

HGFHepatocyte growth factor

ILInterleukin

INFγInterferon-γ

mAbsMonoclonal antibodies

mRNAsMessenger RNAs

MSCsMesenchymal stem cells

NPCNon-parenchymal liver cells

ssDNASingle-stranded DNA

TEMTransmission electron microscopy

TGFβTransforming growth factor-β

TNFαTumor necrosis factor-α

TregRegulatory T cells

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Author: Ryo Tamura - Shinji Uemoto - Yasuhiko Tabata

Source: https://link.springer.com/







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