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Bone Marrow Cells Mediate Tissue Repair By Producing and Regulating MCP‐1/CCL2
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.582.5
Subject(s) - inflammation , bone marrow , in vivo , ccl2 , secretion , biology , microbiology and biotechnology , monocyte , proinflammatory cytokine , immunology , cancer research , chemokine , endocrinology
Exogenous bone marrow‐derived cells (BMDCs) are promising therapeutic agents for treatment of ischemia and traumatic injury. However, their molecular mechanism of action has not been identified, so we have no rational basis for designing optimal therapies. We investigated whether BMDCs exert their effects by modulating inflammation by taking advantage of the fact that BMDCs from healthy young but not obese diabetic mice stimulate vascular growth. By comparing in vitro secretion and in vivo induction of inflammatory cytokines by BMDCS, we identified a potential mediator of BMDC induced tissue repair, monocyte chemoattractant factor ‐1 (MCP‐1). Knockout mouse studies showed that production of MCP‐1 by exogenous and endogenous BMDCs is essential for BMDC mediated tissue repair, and suggest that MCP‐1 acts by modulating IL‐1b. The data also suggest that MCP‐1 in combination with BMDCs may be a potent therapeutic agent in people with dysfunctional BMDCs or impaired healing, and that it may be possible to predict the therapeutic efficacy of an individual's BMDCs by measuring MCP‐1 secretion by BMDCs. Identification of this key mechanism will facilitate design of clinical protocols utilizing BMDCs.