schliessen

Filtern

 

Bibliotheken

Cover Image

Interleukin-10 Contributes to Therapeutic Effect of Mesenchymal Stem Cells for Acute Liver Failure via Signal Transducer and Activator of Transcription 3 Signaling Pathway

Background：Mesenchymal stem cells （MSCs） transplantation has been proven to have therapeutic potential for acute liver failure （ALF）.However,the mechanism remains controversial.Recently,modulation of inflammation by MSCs has been regarded as a crucial mechanism.The aim of the present study was to ex... Full description

Journal Title: Chinese Medical Journal 2016, Vol.129 (8), p.967-975
Main Author: Ma, Hu-Cheng
Other Authors: Wang, Xin , Wu, Min-Na , Zhao, Xin , Yuan, Xian-Wen , Shi, Xiao-Lei
Format: Electronic Article Electronic Article
Language: English
Subjects:
Activator of Transcription 3 Signaling Pathway
Analysis
Angiogenesis
Animals
Apoptosis
Bone marrow
Care and treatment
Conditioned Medium
Conditioned Medium
Immunoregulation
Liver Disease
Signal Transducer and Activator of Transcription 3 Signaling Pathway
Stem Cell Transplantation
Cytokines
digestive
Genetic transcription
Health aspects
Histology
Hospitals
Immunoregulation
Inflammation
Interleukin-10 - physiology
Interleukins
Laboratory animals
Liver
Liver - pathology
Liver Disease
Liver failure
Liver Failure, Acute - pathology
Liver Failure, Acute - therapy
Male
Medical research
Medical schools
Medicine
Mesenchymal Stem Cell Transplantation
oral
Original
Original Article
Rats
Rats, Sprague-Dawley
Rodents
Signal Transducer
Signal Transducer and Activator of Transcription 3 Signaling Pathway
Signal Transduction - physiology
skin physiology
STAT3 Transcription Factor - physiology
Stem Cell Transplantation
Stem cells
Surgery
Survival analysis
Tumor necrosis factor-TNF
信号转导
信号通路
治疗效果
白细胞介素-10
肝功能
转录激活因子
骨髓间充质干细胞
Publisher: China: Wolters Kluwer - Medknow Publications
ID: ISSN: 0366-6999
Link: https://www.ncbi.nlm.nih.gov/pubmed/27064043
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_doaj_primary_oai_doaj_org_article_d62cc48aeb5d441dad84ccd2f18781be
title: Interleukin-10 Contributes to Therapeutic Effect of Mesenchymal Stem Cells for Acute Liver Failure via Signal Transducer and Activator of Transcription 3 Signaling Pathway
format: Article
creator:
  • Ma, Hu-Cheng
  • Wang, Xin
  • Wu, Min-Na
  • Zhao, Xin
  • Yuan, Xian-Wen
  • Shi, Xiao-Lei
subjects:
  • Activator of Transcription 3 Signaling Pathway
  • Analysis
  • Angiogenesis
  • Animals
  • Apoptosis
  • Bone marrow
  • Care and treatment
  • Conditioned Medium
  • Conditioned Medium
  • Immunoregulation
  • Liver Disease
  • Signal Transducer and Activator of Transcription 3 Signaling Pathway
  • Stem Cell Transplantation
  • Cytokines
  • digestive
  • Genetic transcription
  • Health aspects
  • Histology
  • Hospitals
  • Immunoregulation
  • Inflammation
  • Interleukin-10 - physiology
  • Interleukins
  • Laboratory animals
  • Liver
  • Liver - pathology
  • Liver Disease
  • Liver failure
  • Liver Failure, Acute - pathology
  • Liver Failure, Acute - therapy
  • Male
  • Medical research
  • Medical schools
  • Medicine
  • Mesenchymal Stem Cell Transplantation
  • oral
  • Original
  • Original Article
  • Rats
  • Rats, Sprague-Dawley
  • Rodents
  • Signal Transducer
  • Signal Transducer and Activator of Transcription 3 Signaling Pathway
  • Signal Transduction - physiology
  • skin physiology
  • STAT3 Transcription Factor - physiology
  • Stem Cell Transplantation
  • Stem cells
  • Surgery
  • Survival analysis
  • Tumor necrosis factor-TNF
  • 信号转导
  • 信号通路
  • 治疗效果
  • 白细胞介素-10
  • 肝功能
  • 转录激活因子
  • 骨髓间充质干细胞
ispartof: Chinese Medical Journal, 2016, Vol.129 (8), p.967-975
description: Background：Mesenchymal stem cells （MSCs） transplantation has been proven to have therapeutic potential for acute liver failure （ALF）.However,the mechanism remains controversial.Recently,modulation of inflammation by MSCs has been regarded as a crucial mechanism.The aim of the present study was to explore the soluble cytokines secreted by MSCs and their therapeutic effects in ALF.Methods：MSCs isolated from Sprague-Dawley rats were identified by fluorescence-activated cell sorting analysis.Conditioned medium derived from MSCs （MSCs-CM） was collected and analyzed by a cytokine microarray.MSCs and MSCs-CM were transplanted into rats with D-galactosamine-induced ALF.Liver function,survival rate,histology,and inflammatory factors were determined.Exogenous recombinant rat interleukin （IL）-10,anti-rat IL-10 antibody,and AG490 （signal transducer and activator of transcription 3 [STAT3] signaling pathway inhibitor） were administered to explore the therapeutic mechanism of MSCs-CM.Statistical analysis was performed with SPSS version 19.0,and all data were analyzed by the independent-sample t-test.Results：There are statistical differences of the survival curve between ALF＋MSCs group and ALF＋Dulbecco＆#39;s modified Eagle＆#39;s medium （DMEM） group,as well as ALF＋MSCs-CM group and ALF＋DMEM group （all P 〈 0.05）.Serum alanine aminotransferase （ALT） level in the ALF＋MSCs and ALF＋MSCs-CM groups was lower than that in the ALF＋DMEM group （865.53＆#177;52.80 vs.1709.75＆#177;372.12 U/L and 964.72＆#177;414.59 vs.1709.75＆#177;372.12 U/L,respectively,all P 〈 0.05）;meanwhile,serum aspartate aminotransferase （AST） level in the ALF＋MSCs and ALF＋MSCs-CM groups was lower than that in the ALF＋DMEM group （2440.83＆#177;511.94 vs.4234.35＆#177;807.30 U/L and 2739.83＆#177;587.33 vs.4234.35＆#177;807.30 U/L,respectively,all P 〈 0.05）.Furthermore,MSCs or MSCs-CM treatment significantly reduced serum interferon-γ （IFN-γ）,IL-1β,IL-6 levels and increased serum IL-10 level compared with DMEM （all P 〈 0.05）.Proteome profile analysis of MSCs-CM indicated the presence of anti-inflammatory factors and IL-l 0 was the most distinct.Blocking of IL-10 confirmed the therapeutic significance of this cytokine.Phosphorylated STAT3 was upregulated after IL-l 0 infusion and inhibition of STAT3 by AG490 reversed the therapeutic effect of IL-10.Conclusions：The factors released by MSCs,especially IL-10,have the potential for therapeutic recovery of ALF,and the STAT3 signaling pathway may mediate the anti-inflammatory
language: eng
source:
identifier: ISSN: 0366-6999
fulltext: no_fulltext
issn:
  • 0366-6999
  • 2542-5641
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.4125223
LOCALfalse
PrimoNMBib
record
control
sourceidwanfang_jour_doaj_
recordidTN_cdi_doaj_primary_oai_doaj_org_article_d62cc48aeb5d441dad84ccd2f18781be
sourceformatXML
sourcesystemPC
galeidA449083686
cqvip_id668652126
wanfj_idzhcmj201608014
sourcerecordidzhcmj201608014
originalsourceidFETCH-LOGICAL-1619u-34f1dd73078abbf8f939c4009a4f9344870a5cd86df4a37d073093838cd3ba340
addsrcrecordideNptk11v0zAYhSMEYmNwzxWyQELcdNix49g3k0a1waTxIW1cW2_80bpL7c5JWo2_xJ_EXbuyIpSLRPY5T94c5xTFa4KPGcH0I6acj7iU8pjUspbsSXFYVqwcVZyRp8XhbvugeNF1M4zLqqr58-KgrDFnmNHD4vdF6G1q7XDjw4hgNI6hT74ZetuhPqLrqU2wsEPvNTpzzuoeRYe-2s4GPb2bQ4uuejtHY9u2HXIxoVOdrejSL21C5-DbIVm09ICu_CRk9XWC0JlB510IJqt7v4Q--zL1fk8nv-h9DIhuLT5M0A_opyu4e1k8c9B29tX2flT8PD-7Hn8ZXX7_fDE-vRwRTuQwoswRY2qKawFN44STVGqGsQSWHxkTNYZKG8GNY0Brg7NUUkGFNrQByvBRcbHhmggztUh-DulORfDqfiGmiYKUE2mtMrzUmgmwTWUYIwaMYFqb0hFRC9LYzDrZsBZDM7dG2xwvtHvQ_Z3gp2oSl4oJSipKM-DbBhAXNoBPdn-gYHtlrBkWauUUxkRVFGMABpjVhhontAatdeWgJKapBMnA9xvgCoKDMFGzOKQcdKd-TfV8VmLCscBkHcOH7egp3g6269XcdzqfNAQbh04RQUgpsZQ8S9_9I91BiSyrEuOc-1_VBHJ0PriYv1ivoeqUMYkF5WLNOv6PKl_Gzr2OwTqf1_cMeGPQKXZdsm6XEMFqXRO17oFa90BtapItbx6fys7w0Iss-LQNKba5H91NO6xsUll7E-JqDzx6BFaS1-qhURnydjvYNIbJbf6Tdy_iefCqJCXHfwDI9S4X
sourcetypeOpen Website
isCDItrue
recordtypearticle
pqid1925200344
display
typearticle
titleInterleukin-10 Contributes to Therapeutic Effect of Mesenchymal Stem Cells for Acute Liver Failure via Signal Transducer and Activator of Transcription 3 Signaling Pathway
creatorMa, Hu-Cheng ; Wang, Xin ; Wu, Min-Na ; Zhao, Xin ; Yuan, Xian-Wen ; Shi, Xiao-Lei
creatorcontribMa, Hu-Cheng ; Wang, Xin ; Wu, Min-Na ; Zhao, Xin ; Yuan, Xian-Wen ; Shi, Xiao-Lei
descriptionBackground：Mesenchymal stem cells （MSCs） transplantation has been proven to have therapeutic potential for acute liver failure （ALF）.However,the mechanism remains controversial.Recently,modulation of inflammation by MSCs has been regarded as a crucial mechanism.The aim of the present study was to explore the soluble cytokines secreted by MSCs and their therapeutic effects in ALF.Methods：MSCs isolated from Sprague-Dawley rats were identified by fluorescence-activated cell sorting analysis.Conditioned medium derived from MSCs （MSCs-CM） was collected and analyzed by a cytokine microarray.MSCs and MSCs-CM were transplanted into rats with D-galactosamine-induced ALF.Liver function,survival rate,histology,and inflammatory factors were determined.Exogenous recombinant rat interleukin （IL）-10,anti-rat IL-10 antibody,and AG490 （signal transducer and activator of transcription 3 [STAT3] signaling pathway inhibitor） were administered to explore the therapeutic mechanism of MSCs-CM.Statistical analysis was performed with SPSS version 19.0,and all data were analyzed by the independent-sample t-test.Results：There are statistical differences of the survival curve between ALF＋MSCs group and ALF＋Dulbecco＆#39;s modified Eagle＆#39;s medium （DMEM） group,as well as ALF＋MSCs-CM group and ALF＋DMEM group （all P 〈 0.05）.Serum alanine aminotransferase （ALT） level in the ALF＋MSCs and ALF＋MSCs-CM groups was lower than that in the ALF＋DMEM group （865.53＆#177;52.80 vs.1709.75＆#177;372.12 U/L and 964.72＆#177;414.59 vs.1709.75＆#177;372.12 U/L,respectively,all P 〈 0.05）;meanwhile,serum aspartate aminotransferase （AST） level in the ALF＋MSCs and ALF＋MSCs-CM groups was lower than that in the ALF＋DMEM group （2440.83＆#177;511.94 vs.4234.35＆#177;807.30 U/L and 2739.83＆#177;587.33 vs.4234.35＆#177;807.30 U/L,respectively,all P 〈 0.05）.Furthermore,MSCs or MSCs-CM treatment significantly reduced serum interferon-γ （IFN-γ）,IL-1β,IL-6 levels and increased serum IL-10 level compared with DMEM （all P 〈 0.05）.Proteome profile analysis of MSCs-CM indicated the presence of anti-inflammatory factors and IL-l 0 was the most distinct.Blocking of IL-10 confirmed the therapeutic significance of this cytokine.Phosphorylated STAT3 was upregulated after IL-l 0 infusion and inhibition of STAT3 by AG490 reversed the therapeutic effect of IL-10.Conclusions：The factors released by MSCs,especially IL-10,have the potential for therapeutic recovery of ALF,and the STAT3 signaling pathway may mediate the anti-inflammatory effect of IL-10.
identifier
0ISSN: 0366-6999
1EISSN: 2542-5641
2DOI: 10.4103/0366-6999.179794
3PMID: 27064043
languageeng
publisherChina: Wolters Kluwer - Medknow Publications
subjectActivator of Transcription 3 Signaling Pathway ; Analysis ; Angiogenesis ; Animals ; Apoptosis ; Bone marrow ; Care and treatment ; Conditioned Medium ; Conditioned Medium; Immunoregulation; Liver Disease; Signal Transducer and Activator of Transcription 3 Signaling Pathway; Stem Cell Transplantation ; Cytokines ; digestive ; Genetic transcription ; Health aspects ; Histology ; Hospitals ; Immunoregulation ; Inflammation ; Interleukin-10 - physiology ; Interleukins ; Laboratory animals ; Liver ; Liver - pathology ; Liver Disease ; Liver failure ; Liver Failure, Acute - pathology ; Liver Failure, Acute - therapy ; Male ; Medical research ; Medical schools ; Medicine ; Mesenchymal Stem Cell Transplantation ; oral ; Original ; Original Article ; Rats ; Rats, Sprague-Dawley ; Rodents ; Signal Transducer ; Signal Transducer and Activator of Transcription 3 Signaling Pathway ; Signal Transduction - physiology ; skin physiology ; STAT3 Transcription Factor - physiology ; Stem Cell Transplantation ; Stem cells ; Surgery ; Survival analysis ; Tumor necrosis factor-TNF ; 信号转导 ; 信号通路 ; 治疗效果 ; 白细胞介素-10 ; 肝功能 ; 转录激活因子 ; 骨髓间充质干细胞
ispartofChinese Medical Journal, 2016, Vol.129 (8), p.967-975
rights
0COPYRIGHT 2016 Medknow Publications and Media Pvt. Ltd.
1Copyright Medknow Publications & Media Pvt. Ltd. Apr 20, 2016
2Copyright © Wanfang Data Co. Ltd. All Rights Reserved.
3Copyright: © 2016 Chinese Medical Journal 2016
lds50peer_reviewed
oafree_for_read
citesFETCH-LOGICAL-1619u-34f1dd73078abbf8f939c4009a4f9344870a5cd86df4a37d073093838cd3ba340
links
openurl$$Topenurl_article
thumbnail$$Uhttp://image.cqvip.com/vip1000/qk/85656X/85656X.jpg
backlink$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27064043$$D View this record in MEDLINE/PubMed
search
creatorcontrib
0Ma, Hu-Cheng
1Wang, Xin
2Wu, Min-Na
3Zhao, Xin
4Yuan, Xian-Wen
5Shi, Xiao-Lei
title
0Interleukin-10 Contributes to Therapeutic Effect of Mesenchymal Stem Cells for Acute Liver Failure via Signal Transducer and Activator of Transcription 3 Signaling Pathway
1Chinese Medical Journal
addtitleChinese Medical Journal
descriptionBackground：Mesenchymal stem cells （MSCs） transplantation has been proven to have therapeutic potential for acute liver failure （ALF）.However,the mechanism remains controversial.Recently,modulation of inflammation by MSCs has been regarded as a crucial mechanism.The aim of the present study was to explore the soluble cytokines secreted by MSCs and their therapeutic effects in ALF.Methods：MSCs isolated from Sprague-Dawley rats were identified by fluorescence-activated cell sorting analysis.Conditioned medium derived from MSCs （MSCs-CM） was collected and analyzed by a cytokine microarray.MSCs and MSCs-CM were transplanted into rats with D-galactosamine-induced ALF.Liver function,survival rate,histology,and inflammatory factors were determined.Exogenous recombinant rat interleukin （IL）-10,anti-rat IL-10 antibody,and AG490 （signal transducer and activator of transcription 3 [STAT3] signaling pathway inhibitor） were administered to explore the therapeutic mechanism of MSCs-CM.Statistical analysis was performed with SPSS version 19.0,and all data were analyzed by the independent-sample t-test.Results：There are statistical differences of the survival curve between ALF＋MSCs group and ALF＋Dulbecco＆#39;s modified Eagle＆#39;s medium （DMEM） group,as well as ALF＋MSCs-CM group and ALF＋DMEM group （all P 〈 0.05）.Serum alanine aminotransferase （ALT） level in the ALF＋MSCs and ALF＋MSCs-CM groups was lower than that in the ALF＋DMEM group （865.53＆#177;52.80 vs.1709.75＆#177;372.12 U/L and 964.72＆#177;414.59 vs.1709.75＆#177;372.12 U/L,respectively,all P 〈 0.05）;meanwhile,serum aspartate aminotransferase （AST） level in the ALF＋MSCs and ALF＋MSCs-CM groups was lower than that in the ALF＋DMEM group （2440.83＆#177;511.94 vs.4234.35＆#177;807.30 U/L and 2739.83＆#177;587.33 vs.4234.35＆#177;807.30 U/L,respectively,all P 〈 0.05）.Furthermore,MSCs or MSCs-CM treatment significantly reduced serum interferon-γ （IFN-γ）,IL-1β,IL-6 levels and increased serum IL-10 level compared with DMEM （all P 〈 0.05）.Proteome profile analysis of MSCs-CM indicated the presence of anti-inflammatory factors and IL-l 0 was the most distinct.Blocking of IL-10 confirmed the therapeutic significance of this cytokine.Phosphorylated STAT3 was upregulated after IL-l 0 infusion and inhibition of STAT3 by AG490 reversed the therapeutic effect of IL-10.Conclusions：The factors released by MSCs,especially IL-10,have the potential for therapeutic recovery of ALF,and the STAT3 signaling pathway may mediate the anti-inflammatory effect of IL-10.
subject
0Activator of Transcription 3 Signaling Pathway
1Analysis
2Angiogenesis
3Animals
4Apoptosis
5Bone marrow
6Care and treatment
7Conditioned Medium
8Conditioned Medium; Immunoregulation; Liver Disease; Signal Transducer and Activator of Transcription 3 Signaling Pathway; Stem Cell Transplantation
9Cytokines
10digestive
11Genetic transcription
12Health aspects
13Histology
14Hospitals
15Immunoregulation
16Inflammation
17Interleukin-10 - physiology
18Interleukins
19Laboratory animals
20Liver
21Liver - pathology
22Liver Disease
23Liver failure
24Liver Failure, Acute - pathology
25Liver Failure, Acute - therapy
26Male
27Medical research
28Medical schools
29Medicine
30Mesenchymal Stem Cell Transplantation
31oral
32Original
33Original Article
34Rats
35Rats, Sprague-Dawley
36Rodents
37Signal Transducer
38Signal Transducer and Activator of Transcription 3 Signaling Pathway
39Signal Transduction - physiology
40skin physiology
41STAT3 Transcription Factor - physiology
42Stem Cell Transplantation
43Stem cells
44Surgery
45Survival analysis
46Tumor necrosis factor-TNF
47信号转导
48信号通路
49治疗效果
50白细胞介素-10
51肝功能
52转录激活因子
53骨髓间充质干细胞
issn
00366-6999
12542-5641
fulltextfalse
rsrctypearticle
creationdate2016
recordtypearticle
recordideNptk11v0zAYhSMEYmNwzxWyQELcdNix49g3k0a1waTxIW1cW2_80bpL7c5JWo2_xJ_EXbuyIpSLRPY5T94c5xTFa4KPGcH0I6acj7iU8pjUspbsSXFYVqwcVZyRp8XhbvugeNF1M4zLqqr58-KgrDFnmNHD4vdF6G1q7XDjw4hgNI6hT74ZetuhPqLrqU2wsEPvNTpzzuoeRYe-2s4GPb2bQ4uuejtHY9u2HXIxoVOdrejSL21C5-DbIVm09ICu_CRk9XWC0JlB510IJqt7v4Q--zL1fk8nv-h9DIhuLT5M0A_opyu4e1k8c9B29tX2flT8PD-7Hn8ZXX7_fDE-vRwRTuQwoswRY2qKawFN44STVGqGsQSWHxkTNYZKG8GNY0Brg7NUUkGFNrQByvBRcbHhmggztUh-DulORfDqfiGmiYKUE2mtMrzUmgmwTWUYIwaMYFqb0hFRC9LYzDrZsBZDM7dG2xwvtHvQ_Z3gp2oSl4oJSipKM-DbBhAXNoBPdn-gYHtlrBkWauUUxkRVFGMABpjVhhontAatdeWgJKapBMnA9xvgCoKDMFGzOKQcdKd-TfV8VmLCscBkHcOH7egp3g6269XcdzqfNAQbh04RQUgpsZQ8S9_9I91BiSyrEuOc-1_VBHJ0PriYv1ivoeqUMYkF5WLNOv6PKl_Gzr2OwTqf1_cMeGPQKXZdsm6XEMFqXRO17oFa90BtapItbx6fys7w0Iss-LQNKba5H91NO6xsUll7E-JqDzx6BFaS1-qhURnydjvYNIbJbf6Tdy_iefCqJCXHfwDI9S4X
startdate2016
enddate2016
creator
0Ma, Hu-Cheng
1Wang, Xin
2Wu, Min-Na
3Zhao, Xin
4Yuan, Xian-Wen
5Shi, Xiao-Lei
general
0Wolters Kluwer - Medknow Publications
1Medknow Publications and Media Pvt. Ltd
2Lippincott Williams & Wilkins Ovid Technologies
3Department of Hepatobiliary Surgery, Affliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China%First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China
4Wolters Kluwer
5Medknow Publications & Media Pvt Ltd
scope
02RA
192L
2CQIGP
3W91
4~WA
5CGR
6CUY
7CVF
8ECM
9EIF
10NPM
11AAYXX
12CITATION
133V.
147X7
157XB
1688E
178FI
188FJ
198FK
20ABUWG
21AZQEC
22BENPR
23DWQXO
24FYUFA
25GHDGH
26K9.
27M0S
28M1P
29PIMPY
30PQEST
31PQQKQ
32PQUKI
33PRINS
347X8
352B.
364A8
3792I
3893N
39PSX
40TCJ
41BOBZL
42CLFQK
435PM
44DOAMJ
sort
creationdate2016
titleInterleukin-10 Contributes to Therapeutic Effect of Mesenchymal Stem Cells for Acute Liver Failure via Signal Transducer and Activator of Transcription 3 Signaling Pathway
authorMa, Hu-Cheng ; Wang, Xin ; Wu, Min-Na ; Zhao, Xin ; Yuan, Xian-Wen ; Shi, Xiao-Lei
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-1619u-34f1dd73078abbf8f939c4009a4f9344870a5cd86df4a37d073093838cd3ba340
rsrctypearticles
prefilterarticles
languageeng
creationdate2016
topic
0Activator of Transcription 3 Signaling Pathway
1Analysis
2Angiogenesis
3Animals
4Apoptosis
5Bone marrow
6Care and treatment
7Conditioned Medium
8Conditioned Medium; Immunoregulation; Liver Disease; Signal Transducer and Activator of Transcription 3 Signaling Pathway; Stem Cell Transplantation
9Cytokines
10digestive
11Genetic transcription
12Health aspects
13Histology
14Hospitals
15Immunoregulation
16Inflammation
17Interleukin-10 - physiology
18Interleukins
19Laboratory animals
20Liver
21Liver - pathology
22Liver Disease
23Liver failure
24Liver Failure, Acute - pathology
25Liver Failure, Acute - therapy
26Male
27Medical research
28Medical schools
29Medicine
30Mesenchymal Stem Cell Transplantation
31oral
32Original
33Original Article
34Rats
35Rats, Sprague-Dawley
36Rodents
37Signal Transducer
38Signal Transducer and Activator of Transcription 3 Signaling Pathway
39Signal Transduction - physiology
40skin physiology
41STAT3 Transcription Factor - physiology
42Stem Cell Transplantation
43Stem cells
44Surgery
45Survival analysis
46Tumor necrosis factor-TNF
47信号转导
48信号通路
49治疗效果
50白细胞介素-10
51肝功能
52转录激活因子
53骨髓间充质干细胞
toplevelpeer_reviewed
creatorcontrib
0Ma, Hu-Cheng
1Wang, Xin
2Wu, Min-Na
3Zhao, Xin
4Yuan, Xian-Wen
5Shi, Xiao-Lei
collection
0中文科技期刊数据库
1中文科技期刊数据库-CALIS站点
2中文科技期刊数据库-7.0平台
3中文科技期刊数据库-医药卫生
4中文科技期刊数据库- 镜像站点
5Medline
6MEDLINE
7MEDLINE (Ovid)
8MEDLINE
9MEDLINE
10PubMed
11CrossRef
12ProQuest Central (Corporate)
13Health & Medical Collection
14ProQuest Central (purchase pre-March 2016)
15Medical Database (Alumni Edition)
16Hospital Premium Collection
17Hospital Premium Collection (Alumni Edition)
18ProQuest Central (Alumni) (purchase pre-March 2016)
19ProQuest Central (Alumni Edition)
20ProQuest Central Essentials
21ProQuest Central
22ProQuest Central Korea
23Health Research Premium Collection
24Health Research Premium Collection (Alumni)
25ProQuest Health & Medical Complete (Alumni)
26Health & Medical Collection (Alumni Edition)
27Medical Database
28Publicly Available Content Database
29ProQuest One Academic Eastern Edition
30ProQuest One Academic
31ProQuest One Academic UKI Edition
32ProQuest Central China
33MEDLINE - Academic
34Wanfang Data Journals - Hong Kong
35WANFANG Data Centre
36Wanfang Data Journals
37万方数据期刊 - 香港版
38China Online Journals (COJ)
39China Online Journals (COJ)
40OpenAIRE (Open Access)
41OpenAIRE
42PubMed Central (Full Participant titles)
43DOAJ Directory of Open Access Journals
jtitleChinese Medical Journal
delivery
delcategoryRemote Search Resource
fulltextno_fulltext
addata
au
0Ma, Hu-Cheng
1Wang, Xin
2Wu, Min-Na
3Zhao, Xin
4Yuan, Xian-Wen
5Shi, Xiao-Lei
formatjournal
genrearticle
ristypeJOUR
atitleInterleukin-10 Contributes to Therapeutic Effect of Mesenchymal Stem Cells for Acute Liver Failure via Signal Transducer and Activator of Transcription 3 Signaling Pathway
jtitleChinese Medical Journal
addtitleChinese Medical Journal
date2016
risdate2016
volume129
issue8
spage967
epage975
pages967-975
issn0366-6999
eissn2542-5641
notes
0Background：Mesenchymal stem cells （MSCs） transplantation has been proven to have therapeutic potential for acute liver failure （ALF）.However,the mechanism remains controversial.Recently,modulation of inflammation by MSCs has been regarded as a crucial mechanism.The aim of the present study was to explore the soluble cytokines secreted by MSCs and their therapeutic effects in ALF.Methods：MSCs isolated from Sprague-Dawley rats were identified by fluorescence-activated cell sorting analysis.Conditioned medium derived from MSCs （MSCs-CM） was collected and analyzed by a cytokine microarray.MSCs and MSCs-CM were transplanted into rats with D-galactosamine-induced ALF.Liver function,survival rate,histology,and inflammatory factors were determined.Exogenous recombinant rat interleukin （IL）-10,anti-rat IL-10 antibody,and AG490 （signal transducer and activator of transcription 3 [STAT3] signaling pathway inhibitor） were administered to explore the therapeutic mechanism of MSCs-CM.Statistical analysis was performed with SPSS version 19.0,and all data were analyzed by the independent-sample t-test.Results：There are statistical differences of the survival curve between ALF＋MSCs group and ALF＋Dulbecco＆#39;s modified Eagle＆#39;s medium （DMEM） group,as well as ALF＋MSCs-CM group and ALF＋DMEM group （all P 〈 0.05）.Serum alanine aminotransferase （ALT） level in the ALF＋MSCs and ALF＋MSCs-CM groups was lower than that in the ALF＋DMEM group （865.53＆#177;52.80 vs.1709.75＆#177;372.12 U/L and 964.72＆#177;414.59 vs.1709.75＆#177;372.12 U/L,respectively,all P 〈 0.05）;meanwhile,serum aspartate aminotransferase （AST） level in the ALF＋MSCs and ALF＋MSCs-CM groups was lower than that in the ALF＋DMEM group （2440.83＆#177;511.94 vs.4234.35＆#177;807.30 U/L and 2739.83＆#177;587.33 vs.4234.35＆#177;807.30 U/L,respectively,all P 〈 0.05）.Furthermore,MSCs or MSCs-CM treatment significantly reduced serum interferon-γ （IFN-γ）,IL-1β,IL-6 levels and increased serum IL-10 level compared with DMEM （all P 〈 0.05）.Proteome profile analysis of MSCs-CM indicated the presence of anti-inflammatory factors and IL-l 0 was the most distinct.Blocking of IL-10 confirmed the therapeutic significance of this cytokine.Phosphorylated STAT3 was upregulated after IL-l 0 infusion and inhibition of STAT3 by AG490 reversed the therapeutic effect of IL-10.Conclusions：The factors released by MSCs,especially IL-10,have the potential for therapeutic recovery of ALF,and the STAT3 signaling pathway may mediate the anti-inflammatory effect of IL-10.
111-2154/R
2Conditioned Medium; Immunoregulatiom Liver Disease; Signal Transducer and Activator of Transcription 3 Signaling Pathway; Stein Cell Transplantation
abstractBackground：Mesenchymal stem cells （MSCs） transplantation has been proven to have therapeutic potential for acute liver failure （ALF）.However,the mechanism remains controversial.Recently,modulation of inflammation by MSCs has been regarded as a crucial mechanism.The aim of the present study was to explore the soluble cytokines secreted by MSCs and their therapeutic effects in ALF.Methods：MSCs isolated from Sprague-Dawley rats were identified by fluorescence-activated cell sorting analysis.Conditioned medium derived from MSCs （MSCs-CM） was collected and analyzed by a cytokine microarray.MSCs and MSCs-CM were transplanted into rats with D-galactosamine-induced ALF.Liver function,survival rate,histology,and inflammatory factors were determined.Exogenous recombinant rat interleukin （IL）-10,anti-rat IL-10 antibody,and AG490 （signal transducer and activator of transcription 3 [STAT3] signaling pathway inhibitor） were administered to explore the therapeutic mechanism of MSCs-CM.Statistical analysis was performed with SPSS version 19.0,and all data were analyzed by the independent-sample t-test.Results：There are statistical differences of the survival curve between ALF＋MSCs group and ALF＋Dulbecco＆#39;s modified Eagle＆#39;s medium （DMEM） group,as well as ALF＋MSCs-CM group and ALF＋DMEM group （all P 〈 0.05）.Serum alanine aminotransferase （ALT） level in the ALF＋MSCs and ALF＋MSCs-CM groups was lower than that in the ALF＋DMEM group （865.53＆#177;52.80 vs.1709.75＆#177;372.12 U/L and 964.72＆#177;414.59 vs.1709.75＆#177;372.12 U/L,respectively,all P 〈 0.05）;meanwhile,serum aspartate aminotransferase （AST） level in the ALF＋MSCs and ALF＋MSCs-CM groups was lower than that in the ALF＋DMEM group （2440.83＆#177;511.94 vs.4234.35＆#177;807.30 U/L and 2739.83＆#177;587.33 vs.4234.35＆#177;807.30 U/L,respectively,all P 〈 0.05）.Furthermore,MSCs or MSCs-CM treatment significantly reduced serum interferon-γ （IFN-γ）,IL-1β,IL-6 levels and increased serum IL-10 level compared with DMEM （all P 〈 0.05）.Proteome profile analysis of MSCs-CM indicated the presence of anti-inflammatory factors and IL-l 0 was the most distinct.Blocking of IL-10 confirmed the therapeutic significance of this cytokine.Phosphorylated STAT3 was upregulated after IL-l 0 infusion and inhibition of STAT3 by AG490 reversed the therapeutic effect of IL-10.Conclusions：The factors released by MSCs,especially IL-10,have the potential for therapeutic recovery of ALF,and the STAT3 signaling pathway may mediate the anti-inflammatory effect of IL-10.
copChina
pubWolters Kluwer - Medknow Publications
pmid27064043
doi10.4103/0366-6999.179794
oafree_for_read