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Paracrine Effect of Bone Marrow Cells on Hypoxia‐Mediated Vascular Growth
Author(s) -
O’Neill Thomas Joseph,
Wamhoff Brian R,
Owens Gary K,
Skalak Thomas C
Publication year - 2006
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.20.4.a716-b
Subject(s) - bone marrow , angiogenesis , population , arteriole , paracrine signalling , pericyte , endocrinology , hypoxia (environmental) , medicine , biology , microbiology and biotechnology , chemistry , endothelial stem cell , microcirculation , receptor , organic chemistry , oxygen , biochemistry , environmental health , in vitro
We have previously demonstrated a population of bone marrow derived cells (BMCs) within mouse skeletal muscle, which reside in a perivascular position and if mobilized by granulocyte‐macrophage colony stimulating factor (GM‐CSF) are capable of augmenting capillary growth without transdifferentiation into endothelial cells. In this study we expanded the scope of our inquiry to also determine the effect of BMCs on collateral vessel growth. While arcade arteriole length within the mouse spinotrapezius muscle was unchanged after 3 weeks of hypoxia (0 2 =10%), GM‐CSF treatment concurrent with the first week of hypoxia resulted in a 22% increase in arcade arteriole length per muscle. This increase coincided with a doubling in the number of round BMCs associated with terminal arterioles. In addition we determined that the largest subset of muscle‐resident BMCs from the muscle tissue stained CD11b+ by flow cytometry, indicating myeloid lineage. After stimulation with hypoxia, muscle‐resident CD11b+ BMCs contained significantly higher intracellular levels of VEGF, matrix metalloproteinase‐9, and PDGF. Finally, mice transplanted with bone marrow deficient in CD18, used for adhesion and emigration by circulating cells, displayed a trend (p = .16) toward decreased hypoxia‐mediated angiogenesis associated with diminished recruitment of BMCs to the muscle tissue. These observations further support our hypothesis of a paracrine role for BMCs during physiologic angiogenesis. Supported by NIH HL65958 and 5T32 HL007284