title: Up-regulation of CXCR4 in rat umbilical mesenchymal stem cells induced by serum from rat with acute liver failure promotes stem cells migration to injured liver tissue.
abstract: The role of C-X-C chemokine receptor type 4 (CXCR4) in umbilical mesenchymal stem cells (UMSCs) as therapy for liver disease is ill understood. The aim of the study was to evaluate rat UMSCs (rUMSCs) on CXCR4 expression and homing to injured liver tissue. rUMSCs were isolated from umbilical cords of pregnant rats. Acute liver failure (ALF) models were developed using D-galactosamine. CXCR4 expression induction by serum from rats with ALF (LFS), cytokines, growth factors, and LPS was analyzed. CXCR4 expression was analyzed by RT-PCR, western blot, and flow cytometry. rUMSCs were labeled with carboxyfluorescein and pretreated with LFS to induce CXCR4 expression and were transplanted into ALF rats. Animals were sacrificed 48 h and 1 week after transplantation. Liver-homing rUMSCs were observed under fluorescence microscopy. rUMSCs were successfully isolated, expressing CD90 and CD106, but not CD34 and CD45. mRNA and protein expressions of CXCR4 were strongly up-regulated by LFS and by the mixture of cytokines, stem cell factor, and LPS (CM). Expression of cell surface CXCR4 on rUMSCs in groups treated with LFS (42.37 ± 1.60 %) and CM (40.17 ± 1.78 %) was higher than that in the untreated control group (9.67 ± 1.06 %) (both P < 0.001). At 48 h after transplantation, more rUMSCs pretreated with LFS appeared in the portal area, and migrated to the liver parenchyma after 1 week. LFS strongly induced the surface expression of CXCR4 on rUMSCs. Increasing CXCR4 expression on rUMSCs may enhance their homing ability to injured liver tissue, and may eventually be used for treating liver diseases.
authors.affiliation: Department of Infectious Diseases, First Hospital Affiliated to Suzhou University, Suzhou, 215006, Jiangsu, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Deng
authors.forename: Ailan
authors.initials: A
authors.lastname: Qin
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhao
authors.forename: Tingting
authors.initials: T
authors.lastname: Feng
authors.forename: Cuicui
authors.initials: C
authors.lastname: Shi
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D017114:Liver Failure, Acute / Q000097:blood* / Q000209:etiology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D044967:Serum / Q000502:physiology; D015854:Up-Regulation
chemical_list: C486264:Cxcr4 protein, rat; D016207:Cytokines; D019718:Receptors, CXCR4
references.citation: Neurochem Res. 2011 Dec;36(12):2391-400
references.pmid: 21877237
references.citation: Lancet. 2003 Aug 30;362(9385):697-703
references.pmid: 12957092
references.citation: Am J Med Sci. 2011 Sep;342(3):212-7
references.pmid: 21642820
references.citation: Haematologica. 2007 Jul;92(7):897-904
references.pmid: 17606439
references.citation: Cancer Res. 2009 Mar 1;69(5):1815-20
references.pmid: 19244122
references.citation: J Exp Med. 2005 Apr 18;201(8):1307-18
references.pmid: 15837815
references.citation: Cytotherapy. 2006;8(4):315-7
references.pmid: 16923606
references.citation: Curr Opin Organ Transplant. 2011 Feb;16(1):69-75
references.pmid: 21150616
references.citation: Gut. 2007 Mar;56(3):405-15
references.pmid: 16928726
references.citation: Nat Protoc. 2010 Apr;5(4):617-27
references.pmid: 20224562
references.citation: Leukemia. 2002 Oct;16(10):1992-2003
references.pmid: 12357350
references.citation: J Autoimmun. 2008 Aug;31(1):7-12
references.pmid: 18442895
references.citation: Stem Cells. 2006 Apr;24(4):1030-41
references.pmid: 16253981
references.citation: Cardiovasc Revasc Med. 2006 Jan-Mar;7(1):19-24
references.pmid: 16513519
references.citation: Hepatobiliary Pancreat Dis Int. 2012 Aug 15;11(4):360-71
references.pmid: 22893462
references.citation: Hepatology. 2008 May;47(5):1634-43
references.pmid: 18395843
references.citation: Cell Biol Int. 2009 Jul;33(7):772-7
references.pmid: 19427913
references.citation: PLoS One. 2007 Sep 26;2(9):e941
references.pmid: 17895982
references.citation: Curr Opin Organ Transplant. 2009 Dec;14(6):667-73
references.pmid: 19779345
references.citation: Stem Cells. 2006 May;24(5):1254-64
references.pmid: 16410389
references.citation: Liver Transpl. 2009 May;15(5):484-95
references.pmid: 19399744
references.citation: Toxicol Lett. 2011 Jul 4;204(1):92-9
references.pmid: 21550386
references.citation: Exp Cell Res. 2007 Aug 1;313(13):2875-86
references.pmid: 17574236
references.citation: Blood. 2005 Jul 15;106(2):756-63
references.pmid: 15817682
references.citation: Clin Biochem. 2012 Apr;45(6):385-96
references.pmid: 22306885
references.citation: Hepatology. 2008 Jan;47(1):279-87
references.pmid: 17935178
references.citation: Cytotherapy. 2009;11(5):548-58
references.pmid: 19657806
references.citation: Genes Dev. 2011 Oct 1;25(19):2069-78
references.pmid: 21979919
references.citation: PLoS One. 2008;3(10):e3336
references.pmid: 18852872
references.citation: Stem Cells Dev. 2008 Oct;17(5):993-1003
references.pmid: 18537463
references.citation: Hepatology. 2004 Dec;40(6):1275-84
references.pmid: 15562440
references.citation: Blood. 2003 Sep 15;102(6):1951-8
references.pmid: 12730102
references.citation: Cytotherapy. 2009;11(4):414-26
references.pmid: 19513901
references.citation: Ann Hematol. 2004 Dec;83(12):733-8
references.pmid: 15372203
references.citation: J Natl Cancer Inst. 2005 Dec 21;97(24):1840-7
references.pmid: 16368946
references.citation: Mech Dev. 2003 Jan;120(1):117-30
references.pmid: 12490302
references.citation: J Infect Dis. 1997 Aug;176(2):439-44
references.pmid: 9237710
references.citation: J Cell Biochem. 2013 Jan;114(1):79-88
references.pmid: 22833529
references.citation: Transplant Proc. 2007 Mar;39(2):573-6
references.pmid: 17362785
references.citation: Haematologica. 2008 Oct;93(10):1457-65
references.pmid: 18728032