title: The role of indoleamine 2,3 dioxygenase in beneficial effects of stem cells in hind limb ischemia reperfusion injury.
abstract: Ischemia-Reperfusion (IR) injury of limb remains a significant clinical problem causing secondary complications and restricting clinical recovery, despite rapid restoration of blood flow and successful surgery. In an attempt to further improve post ischemic tissue repair, we investigated the effect of a local administration of bone marrow derived stem cells (BMDSCs) in the presence or absence of immune-regulatory enzyme, IDO, in a murine model. A whole limb warm ischemia-reperfusion model was developed using IDO sufficient (WT) and deficient (KO) mice with C57/BL6 background. Twenty-four hours after injury, 5 × 105 cells (5×105 cells/200 µL of PBS solution) BMDSCs (Sca1 + cells) were injected intramuscularly while the control group received just the vehicle buffer (PBS). Forty-eight to seventy-two hours after limb BMDSC injection, recovery status including the ratio of intrinsic paw function between affected and normal paws, general mobility, and inflammatory responses were measured using video micrometery, flow cytometry, and immunohistochemistry techniques. Additionally, MRI/MRA studies were performed to further study the inflammatory response between groups and to confirm reconstitution of blood flow after ischemia. For the first time, our data, showed that IDO may potentially represent a partial role in triggering the beneficial effects of BMDSCs in faster recovery and protection against structural changes and cellular damage in a hind limb IR injury setting (P = 0.00058).
authors.affiliation: Department of Surgery, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Masoumy
authors.affiliation: Department of Surgery, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Jack
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Oral Biology, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Jun Yao
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Radiology and Imaging, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Nathan
authors.initials: N
authors.lastname: Yanasak
authors.affiliation: Cancer Center, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Middleton
authors.affiliation: Department of Ophthalmology, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Folami
authors.initials: F
authors.lastname: Lamoke
authors.affiliation: Department of Oral Biology, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Mahmood S
authors.initials: MS
authors.lastname: Mozaffari
authors.affiliation: Department of Surgery, Georgia Regents University, Augusta, Georgia, United States of America; Department of Oral Biology, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Babak
authors.initials: B
authors.lastname: Baban
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005434:Flow Cytometry; D006614:Hindlimb / Q000473:pathology*; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000628:therapy*; D013234:Stem Cells / Q000502:physiology*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase
references.citation: J Immunol. 2005 Nov 1;175(9):5601-5
references.pmid: 16237046
references.citation: J Immunol. 2000 Apr 1;164(7):3596-9
references.pmid: 10725715
references.citation: Int J Biochem Cell Biol. 2009 Mar;41(3):467-71
references.pmid: 18282734
references.citation: Blood. 2002 May 15;99(10):3838-43
references.pmid: 11986244
references.citation: Stem Cells. 2009 Apr;27(4):909-19
references.pmid: 19353519
references.citation: Exp Mol Med. 2009 May 31;41(5):315-24
references.pmid: 19307751
references.citation: Plast Reconstr Surg. 2013 Nov;132(5):1173-1180
references.pmid: 24165599
references.citation: Int J Biomed Sci. 2007 Jun;3(2):76-80
references.pmid: 23675026
references.citation: Cell Mol Immunol. 2006 Aug;3(4):271-7
references.pmid: 16978535
references.citation: Mol Pharmacol. 2011 Oct;80(4):673-82
references.pmid: 21791576
references.citation: Science. 1998 Aug 21;281(5380):1191-3
references.pmid: 9712583
references.citation: Stem Cells Int. 2012;2012:392050
references.pmid: 23319959
references.citation: Cardiovasc Surg. 2002 Dec;10(6):620-30
references.pmid: 12453699
references.citation: J Immunol. 2011 Sep 1;187(5):2329-35
references.pmid: 21813777
references.citation: Curr Opin Immunol. 2006 Apr;18(2):220-5
references.pmid: 16460921
references.citation: Am J Physiol Regul Integr Comp Physiol. 2012 Dec;303(11):R1136-46
references.pmid: 23100028
references.citation: Nat Med. 2011 Nov 07;17(11):1391-401
references.pmid: 22064429
references.citation: J Cell Physiol. 2007 Apr;211(1):27-35
references.pmid: 17226788
references.citation: Proc Natl Acad Sci U S A. 1984 Feb;81(3):908-12
references.pmid: 6422465
references.citation: Adv Exp Med Biol. 2003;527:27-35
references.pmid: 15206713
references.citation: J Immunol. 2009 Aug 15;183(4):2475-83
references.pmid: 19635913
references.citation: Immunology. 2012 Nov;137(3):206-13
references.pmid: 22804624
references.citation: J Clin Invest. 2007 Sep;117(9):2570-82
references.pmid: 17710230
references.citation: Cytotherapy. 2005;7(1):36-45
references.pmid: 16040382
references.citation: Infect Immun. 2001 Oct;69(10):6527-31
references.pmid: 11553600
references.citation: Am J Transplant. 2006 Apr;6(4):652-8
references.pmid: 16539620
references.citation: Exp Hematol. 2002 Jan;30(1):42-8
references.pmid: 11823036
references.citation: J Clin Invest. 2004 Jul;114(2):280-90
references.pmid: 15254595
references.citation: Circ Res. 2008 Nov 21;103(11):1204-19
references.pmid: 19028920
references.citation: Cell Immunol. 2012;272(2):112-6
references.pmid: 22138499
references.citation: Stem Cells. 2010 Mar 31;28(3):585-96
references.pmid: 19967788
references.citation: J Neuroimmunol. 2008 Jan;193(1-2):12-23
references.pmid: 18077006
references.citation: Cancer Res. 2007 Aug 1;67(15):7082-7
references.pmid: 17671174
references.citation: Mayo Clin Proc. 2003 Aug;78(8):993-1003
references.pmid: 12911047
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2611-6
references.pmid: 16477023
references.citation: Trends Immunol. 2012 Mar;33(3):136-43
references.pmid: 22227317
references.citation: Annu Rev Immunol. 1993;11:129-63
references.pmid: 8476559
references.citation: PLoS One. 2011 Feb 16;6(2):e14698
references.pmid: 21359206
references.citation: Nat Med. 2003 Oct;9(10):1269-74
references.pmid: 14502282
references.citation: J Reprod Immunol. 2004 Apr;61(2):67-77
references.pmid: 15063630