Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells.
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.
Rajantie
Iiro
I
Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Ilmonen
Maritta
M
Alminaite
Agne
A
Ozerdem
Ugur
U
Alitalo
Kari
K
Salven
Petri
P
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
D039481:CD11b Antigen; D010455:Peptides; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D017493:Leukocyte Common Antigens