title: Lin- cells mediate tissue repair by regulating MCP-1/CCL-2.
abstract: Exogenous bone marrow-derived cells (BMDCs) are promising therapeutic agents for the treatment of tissue ischemia and traumatic injury. However, until we identify the molecular mechanisms that underlie their actions, there can be no rational basis for the design of therapeutic strategies using BMDCs. The pro-healing effects of BMDCs are apparent very shortly after treatment, which suggests that they may exert their effects by the modulation of acute inflammation. We investigated this hypothesis by taking advantage of the fact that BMDCs from healthy, young, but not obese, diabetic mice stimulate vascular growth. By comparing both in vitro secretion and in vivo local induction of acute phase inflammatory cytokines by these cells, we identified monocyte chemoattractant factor 1 and tumor necrosis factor α as potential mediators of BMDC-induced tissue repair. In vivo analysis of BMDC-treated ischemic limbs and cutaneous wounds revealed that the production of monocyte chemoattractant factor 1 by exogenous and endogenous BMDCs is essential for BMDC-mediated vascular growth and tissue healing, while the inability of BMDCs to produce tumor necrosis factor α appears to play a lesser but still meaningful role. Thus, measurements of the secretion of cytokines by BMDCs may allow us to identify a priori individuals who would or would not be good candidates for BMDC-based therapies.
authors.affiliation: Departments of Integrative Physiology, The University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Gina C
authors.initials: GC
authors.lastname: Schatteman
authors.forename: Ola
authors.initials: O
authors.lastname: Awad
authors.forename: Eric
authors.initials: E
authors.lastname: Nau
authors.forename: Chunlin
authors.initials: C
authors.lastname: Wang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Jiao
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tomanek
authors.forename: Martine
authors.initials: M
authors.lastname: Dunnwald
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005121:Extremities; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007511:Ischemia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D054411:Receptors, Leptin / Q000378:metabolism*; D012867:Skin / Q000293:injuries; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014945:Wound Healing
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D018836:Inflammation Mediators; D054411:Receptors, Leptin; D014409:Tumor Necrosis Factor-alpha
references.citation: J Surg Res. 2011 Jan;165(1):165-70
references.pmid: 20036386
references.citation: Circulation. 2000 Jul 11;102(2):185-90
references.pmid: 10889129
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Nat Med. 1997 Dec;3(12):1337-45
references.pmid: 9396603
references.citation: J Vasc Res. 2003 Jul-Aug;40(4):368-77
references.pmid: 12891006
references.citation: J Leukoc Biol. 1994 Mar;55(3):410-22
references.pmid: 7509844
references.citation: Circulation. 2001 Jun 19;103(24):2885-90
references.pmid: 11413075
references.citation: J Clin Invest. 1999 May;103(9):1269-76
references.pmid: 10225970
references.citation: Nature. 1996 Feb 15;379(6566):632-5
references.pmid: 8628397
references.citation: J Leukoc Biol. 1995 May;57(5):788-94
references.pmid: 7759959
references.citation: J Exp Med. 1998 Feb 16;187(4):601-8
references.pmid: 9463410
references.citation: J Leukoc Biol. 2001 Apr;69(4):513-21
references.pmid: 11310836
references.citation: Stem Cells. 2001;19(4):304-12
references.pmid: 11463950
references.citation: Circ Res. 2003 Jun 13;92(11):1247-53
references.pmid: 12730094
references.citation: J Clin Invest. 2010 Apr;120(4):1192-203
references.pmid: 20234092
references.citation: Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H2089-96
references.pmid: 16219813
references.citation: J Clin Invest. 2000 Jun;105(11):1527-36
references.pmid: 10841511
references.citation: Arthritis Rheum. 2000 Mar;43(3):608-16
references.pmid: 10728755
references.citation: Ther Adv Cardiovasc Dis. 2010 Feb;4(1):27-42
references.pmid: 20042449
references.citation: Cell. 1996 Feb 9;84(3):491-5
references.pmid: 8608603
references.citation: Regen Med. 2009 Jan;4(1):119-27
references.pmid: 19105621
references.citation: FASEB J. 2004 Aug;18(11):1273-5
references.pmid: 15208264
references.citation: Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1787-93
references.pmid: 19608967
references.citation: J Exp Med. 1996 Oct 1;184(4):1397-411
references.pmid: 8879212
references.citation: Circulation. 2002 Nov 26;106(22):2781-6
references.pmid: 12451003
references.citation: Cell. 1993 Mar 26;72(6):835-46
references.pmid: 7681362
references.citation: Circ Res. 2006 May 12;98(9):1194-202
references.pmid: 16574905
references.citation: Circ Res. 2000 Oct 27;87(9):728-30
references.pmid: 11055974
references.citation: Am J Pathol. 1998 Jun;152(6):1667-79
references.pmid: 9626071
references.citation: Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):758-64
references.pmid: 16410458
references.citation: J Leukoc Biol. 2000 Jul;68(1):1-8
references.pmid: 10914483
references.citation: Mol Ther. 2009 Nov;17(11):1938-47
references.pmid: 19690521
references.citation: J Clin Invest. 2000 Aug;106(4):571-8
references.pmid: 10953032
references.citation: Proc Natl Acad Sci U S A. 1990 Jul;87(13):5134-8
references.pmid: 1695010
references.citation: J Biol Chem. 1991 May 25;266(15):9912-8
references.pmid: 2033076
references.citation: Thromb Haemost. 2010 Apr;103(4):696-709
references.pmid: 20174766
references.citation: J Cell Sci. 1996 May;109 ( Pt 5):1017-28
references.pmid: 8743949
references.citation: FASEB J. 1994 Dec;8(15):1314-25
references.pmid: 8001745
references.citation: J Immunol. 1989 Mar 15;142(6):1956-62
references.pmid: 2921521
references.citation: J Immunol. 2007 Aug 1;179(3):1449-57
references.pmid: 17641010
references.citation: Eur J Cell Biol. 2000 Nov;79(11):850-7
references.pmid: 11139149