title: Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells.
abstract: Bone marrow (BM)-derived cells are thought to participate in the growth of blood vessels during postnatal vascular regeneration and tumor growth, a process previously attributed to stem and precursor cells differentiating to endothelial cells. We used multichannel laser scanning confocal microscopy of whole-mounted tissues to study angiogenesis in chimeric mice created by reconstituting C57BL mice with genetically marked syngeneic BM. We show that BM-derived endothelial cells do not significantly contribute to tumor- or cytokine-induced neoangiogenesis. Instead, BM-derived periendothelial vascular mural cells were persistently detected at sites of tumor- or vascular endothelial growth factor-induced angiogenesis. Subpopulations of these cells expressed the pericyte-specific NG2 proteoglycan, or the hematopoietic markers CD11b and CD45, but did not detectably express the smooth muscle markers smooth muscle alpha-actin or desmin. Thus, the major contribution of the BM to angiogenic processes is not endothelial, but may come from progenitors for periendothelial vascular mural and hematopoietic effector cells.
authors.affiliation: Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Iiro
authors.initials: I
authors.lastname: Rajantie
authors.forename: Maritta
authors.initials: M
authors.lastname: Ilmonen
authors.forename: Agne
authors.initials: A
authors.lastname: Alminaite
authors.forename: Ugur
authors.initials: U
authors.lastname: Ozerdem
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Petri
authors.initials: P
authors.lastname: Salven
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D039481:CD11b Antigen / Q000737:chemistry; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000737:chemistry; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000737:chemistry; D011509:Proteoglycans / Q000737:chemistry; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D010455:Peptides; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D017493:Leukocyte Common Antigens