Lin- cells mediate tissue repair by regulating MCP-1/CCL-2.
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.
Schatteman
Gina C
GC
Departments of Integrative Physiology, The University of Iowa, Iowa City, Iowa 52242, USA.
Awad
Ola
O
Nau
Eric
E
Wang
Chunlin
C
Jiao
Chunhua
C
Tomanek
Robert J
RJ
Dunnwald
Martine
M
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
D018932:Chemokine CCL2; D016207:Cytokines; D018836:Inflammation Mediators; D054411:Receptors, Leptin; D014409:Tumor Necrosis Factor-alpha
J Surg Res. 2011 Jan;165(1):165-70
20036386
Circulation. 2000 Jul 11;102(2):185-90
10889129
Anal Biochem. 1976 May 7;72:248-54
942051
Nat Med. 1997 Dec;3(12):1337-45
9396603
J Vasc Res. 2003 Jul-Aug;40(4):368-77
12891006
J Leukoc Biol. 1994 Mar;55(3):410-22
7509844
Circulation. 2001 Jun 19;103(24):2885-90
11413075
J Clin Invest. 1999 May;103(9):1269-76
10225970
Nature. 1996 Feb 15;379(6566):632-5
8628397
J Leukoc Biol. 1995 May;57(5):788-94
7759959
J Exp Med. 1998 Feb 16;187(4):601-8
9463410
J Leukoc Biol. 2001 Apr;69(4):513-21
11310836
Stem Cells. 2001;19(4):304-12
11463950
Circ Res. 2003 Jun 13;92(11):1247-53
12730094
J Clin Invest. 2010 Apr;120(4):1192-203
20234092
Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H2089-96
16219813
J Clin Invest. 2000 Jun;105(11):1527-36
10841511
Arthritis Rheum. 2000 Mar;43(3):608-16
10728755
Ther Adv Cardiovasc Dis. 2010 Feb;4(1):27-42
20042449
Cell. 1996 Feb 9;84(3):491-5
8608603
Regen Med. 2009 Jan;4(1):119-27
19105621
FASEB J. 2004 Aug;18(11):1273-5
15208264
Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1787-93
19608967
J Exp Med. 1996 Oct 1;184(4):1397-411
8879212
Circulation. 2002 Nov 26;106(22):2781-6
12451003
Cell. 1993 Mar 26;72(6):835-46
7681362
Circ Res. 2006 May 12;98(9):1194-202
16574905
Circ Res. 2000 Oct 27;87(9):728-30
11055974
Am J Pathol. 1998 Jun;152(6):1667-79
9626071
Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):758-64
16410458
J Leukoc Biol. 2000 Jul;68(1):1-8
10914483
Mol Ther. 2009 Nov;17(11):1938-47
19690521
J Clin Invest. 2000 Aug;106(4):571-8
10953032
Proc Natl Acad Sci U S A. 1990 Jul;87(13):5134-8
1695010
J Biol Chem. 1991 May 25;266(15):9912-8
2033076
Thromb Haemost. 2010 Apr;103(4):696-709
20174766
J Cell Sci. 1996 May;109 ( Pt 5):1017-28
8743949
FASEB J. 1994 Dec;8(15):1314-25
8001745
J Immunol. 1989 Mar 15;142(6):1956-62
2921521
J Immunol. 2007 Aug 1;179(3):1449-57
17641010
Eur J Cell Biol. 2000 Nov;79(11):850-7
11139149