Premium
Bone Marrow‐Derived Cells Stimulate Healing by Modulating Early Inflammatory Processes
Author(s) -
Schatteman Gina C,
Jiao Chunhua,
Leymaster Nicholas,
Timpe Josh,
Dunnwald Martine
Publication year - 2010
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.24.1_supplement.175.6
Subject(s) - monocyte , downregulation and upregulation , bone marrow , growth factor , inflammation , immunology , wound healing , proinflammatory cytokine , cell growth , medicine , cancer research , microbiology and biotechnology , biology , receptor , biochemistry , genetics , gene
Improvements in healing and vascular growth from acute exogenous bone marrow‐derived cell (BMDC) therapy are apparent by a few days after injury, suggesting that BMDCs modulate early inflammatory events. That MCP‐1 is essential for BMDC mediated healing supports this hypothesis. To examine BMDC impact on inflammatory processes and subsequent growth factor production, BMDCs from healthy (wt), obese diabetic (db) and monocyte chemoattractant protein‐1 (MCP‐1‐) knockout mice were injected into ischemic mouse hindlimbs. (BMDCs from C57Bl/6 but not db or MCP‐1‐ mice stimulate MCP‐1 production and promote limb healing.) Fewer immunolabeled monocytes (day 3) and neutrophils (day 1) were seen in ischemic limbs treated with BMDCs from db and MCP‐1‐ mice than those that received cells from wt mice. However, levels of six pro‐angiogenic growth factors measured by ELISA at days 1, 3, and 5 did not correlate with the extent of monocyte/neutrophil infiltration or healing. We observed a complex temporally regulated pattern of growth factor expression in ischemic muscle that differed depending on cell treatment, but at all time points for all factors differences were at most 2‐fold. Thus, BMDCs may stimulate healing by an immunomodulatory process that only modestly impacts pro‐angiogenic growth factor expression and that may not require their upregulation to induce vascular growth and healing. Support: NIH DK55965