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Bone marrow progenitor cells do not contribute to liver fibrogenic cells

Bone marrow progenitor cells do not contribute to liver fibrogenic cells

作     者:Bruno Diaz Paredes Lanuza Alaby Pinheiro Faccioli Luiz Fernando Quintanilha Karina Dutra Asensi Camila Zaverucha do Valle Paulo César Canary Christina Maeda Takiya Antonio Carlos Campos de Carvalho Regina Coeli dos Santos Goldenberg 

作者机构:Carlos Chagas Filho Biophysics InstituteRio de Janeiro 21941-902Brazil Radiology DepartmentClementino Fraga Filho University HospitalRio de Janeiro 22909-538Brazil 

出 版 物:《World Journal of Hepatology》 (世界肝病学杂志(英文版)(电子版))

年 卷 期:2012年第4卷第10期

页      面:274-283页

学科分类:1002[医学-临床医学] 100210[医学-外科学(含:普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基  金:Supported by Brazilian Council for Scientific and Technological Development Coordination for the Improvement of Higher Education Personnel Rio de Janeiro State Research Supporting Foundation and Ministry of Health 

主  题:Bone marrow Liver Fibrosis Progenitor cells Chimeric mice Green fluorescent protein+ cells 

摘      要:AIM:To investigate the contribution of bone marrow(BM) cells to hepatic ***:To establish a model of chimerism,C57Bl/6 female mice were subjected to full-body irradiation(7 Gy) resulting in BM *** mononuclear cells obtained from male transgenic mice expressing enhanced green fluorescent protein(GFP) were used for *** was confirmed by flow *** induce liver injury,chimeric animals received carbon tetrachloride(CCl4) 0.5 mL/kg intraperitoneally twice a week for 30 d(CCl4 30 d) and age-matched controls received saline(Saline 30 d).At the end of this period,animals were sacrificed for post mortem *** samples were stained with hematoxylin and eosin to observe liver architectural changes and with Sirius red for collagen quantification by morphometric analysis.α-smooth muscle actin(α-SMA) was analyzed by confocal microscopy to identify GFP+ cells with myofibroblast(MF) *** tissue,BM and peripheral blood were collected and prepared for flow cytometric analysis using specific markers for detection of hepatic stellate cells(HSCs) and precursors from the ***:Injury to the liver induced changes in the hepatic parenchymal architecture,as reflected by the presence of inflammatory infiltrate and an increase in collagen deposition(Saline 30 d = 11.10% ± 1.12% vs CCl4 30 d = 12.60% ± 0.73%,P = 0.0329).Confocal microscopy revealed increased reactivity against α-SMA in CCl4 30 d compared to Saline 30 d,but there was no co-localization with GFP+ cells,suggesting that cells from BM do not differentiate to *** flow cytometric analysis showed a significant increase of CD45+/GFP+ cells in liver tissue(Saline 30 d = 3.2% ± 2.2% vs CCl4 30 d = 5.8% ± 1.3%,P = 0.0458),suggesting that this increase was due to inflammatory cell infiltration(neutrophils and monocytes).There was also a significant increase of common myeloid progenitor cells(CD117+/CD45+) in the livers of CCl4-treated animals(Saline 3

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