title: A systemic provascular response in bone marrow to musculoskeletal trauma in mice.
abstract: Post-natal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells migrate, differentiate and incorporate into the nacent endothelium and thereby contribute to physiological and pathological neurovascularisation, has stimulated much interest. Its contribution to neovascularisation of tumours, wound healing and revascularisation associated with ischaemia of skeletal and cardiac muscles is well established. We evaluated the responses of endothelial precursor cells in bone marrow to musculoskeletal trauma in mice. Bone marrow from six C57 Black 6 mice subjected to a standardised, closed fracture of the femur, was analysed for the combined expression of cell-surface markers stem cell antigen 1 (sca-1(+)) and stem cell factor receptor, CD117 (c-kit(+)) in order to identify the endothelial precursor cell population. Immunomagnetically-enriched sca-1(+) mononuclear cell (MNC(sca-1+)) populations were then cultured and examined for functional vascular endothelial differentiation. Bone marrow MNC(sca-1+,c-kit+) counts increased almost twofold within 48 hours of the event, compared with baseline levels, before decreasing by 72 hours. Sca-1(+) mononuclear cell populations in culture from samples of bone marrow at 48 hours bound together Ulex Europus-1, and incorporated fluorescent 1,1'-dioctadecyl- 3,3,3,'3'-tetramethylindocarbocyanine perchlorate-labelled acetylated low-density lipoprotein intracellularily, both characteristics of mature endothelium. Our findings suggest that a systemic provascular response of bone marrow is initiated by musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of neovascularisation and the healing of fractures.
authors.affiliation: Department of Surgical, Research and Orthopaedic Surgery, Cork University Hospital, Wilton, Cork, Republic of Ireland. alanlaing@eircom.net
authors.forename: A J
authors.initials: AJ
authors.lastname: Laing
authors.forename: J P
authors.initials: JP
authors.lastname: Dillon
authors.forename: E T
authors.initials: ET
authors.lastname: Condon
authors.forename: J C
authors.initials: JC
authors.lastname: Coffey
authors.forename: J T
authors.initials: JT
authors.lastname: Street
authors.forename: J H
authors.initials: JH
authors.lastname: Wang
authors.forename: A J
authors.initials: AJ
authors.lastname: McGuinness
authors.forename: H P
authors.initials: HP
authors.lastname: Redmond
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005264:Femoral Fractures / Q000473:pathology / Q000503:physiopathology*; D018189:Immunomagnetic Separation / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013234:Stem Cells / Q000473:pathology / Q000502:physiology
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit