Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells - PubMed (original) (raw)

Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells

Iiro Rajantie et al. Blood. 2004.

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.

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Figures

Figure 1

Figure 1. Periendothelial location of bone marrow–derived cells in angiogenic vessels

Angiogenesis was induced in the ears of mice that underwent BM transplantation by repeated subcutaneous VEGF protein injections (A) or by subcutaneous implantation of B16 melanoma (B-D). The tissues were studied by immunofluorescence microscopy (C) or by laser scanning confocal microscopy (A-B, D). (A-B) Vascular endothelial cells stained for von Willebrand factor (VWF, A) or CD105 (B) demonstrate the periendothelial location of the GFP+ BM-derived cells. Note that no GFP+ endothelial cells can be detected. (C) The abundant number and close association of BM-derived cells to endothelial cells (CD31 staining, red) can also be seen in the peritumoral area where larger arterioles with no apparent angiogenic activity are seen. (D) A 3-dimensional projection digitally reconstituted from stacks of confocal optical slices demonstrates the periendothelial location of the BM-derived GFP+ cells bordering the vascular endothelial cells expressing VWF (red). Bars represent 40 μm.

Figure 2

Figure 2. Subpopulations of periendothelial BM-derived vascular mural cells express the pericyte marker NG2 proteolygan and/or the hematopoietic markers CD45 or CD11b

Angiogenesis was induced in mice that underwent BM transplantation by subcutaneous implantation of B16 melanoma (A, C-D) or by repeated subcutaneous VEGF protein injections (B), and the tissues were analyzed by confocal microscopy. (A) Some of the BM-derived mural cells covering angiogenic blood vessel endothelium (CD31 staining, blue) express the pericyte marker NG2 (red). (B) A 3-dimensional projection demonstrates that BM-derived GFP+ periendothelial cells encompass both cells expressing CD45 (arrowheads) and cells with no CD45 immunoreactivity (arrows). (C-D) Similarly, BM-derived NG2+ cells also include cells that do not coexpress CD45 or CD11b (arrows). Bars represent 30 μm.

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