Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1–Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells

Abstract

Abstract-Peripheral blood (PB)-derived CD14ϩ monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)-or PB-derived CD34 Ϫ /CD14 ϩ cells are involved in reendothelialization after carotid balloon injury. Although neither hematopoietic nor mesenchymal stem cells were included in human BM-derived CD34 Ϫ /CD14 ϩ monocyte lineage cells (BM-MLCs), they expressed EC-specific markers (Tie2, CD31, VE-cadherin, and endoglin) to an extent identical to mature ECs. When BM-MLCs were cultured with vascular endothelial growth factors, hematopoietic markers were drastically decreased and new EC-specific markers (Flk and CD34) were induced. BM-MLCs were intra-arterially transplanted into balloon-injured arteries of athymic nude rats. When BM-MLCs were activated by monocyte chemoattractant protein-1 (MCP-1) in vivo or in vitro, they adhered onto injured endothelium, differentiated into EC-like cells by losing hematopoietic markers, and inhibited neointimal hyperplasia. Ability to prevent neointimal hyperplasia was more efficient than that of BM-derived CD34

Flow cytometric evaluation of circulating endothelial cells: A new protocol for identifying endothelial cells at several stages of differentiation

“…Therefore, we analyzed ECs in peripheral blood rather than generating cultures. (3) CD133+ or CD34+ cell selection: Cell loss can occur during cell selection by magnetic microbeads [13,28]. ECs can also develop from mesenchymal CD34-progenitor cells [29], and CD133À or CD34À ECs will be excluded by this procedure.…”

“…Thus, EC maturation may occur more rapidly than was previously thought, and the timescale of alterations in maturation may be expressed in hours. Studies in peripheral blood samples from patients with sickle cell disease, which contain a large number of ECs and cytokines, can provide insight into these processes in vitro [28]. Future studies that evaluate the maturation of cells from healthy subjects and in different pathophysiologic conditions may be useful.…”

Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma

“…Macrophages take part into neovascularization through secreting a wide array of angiogenic growth factors, including VEGF and bFGF (Ribatti et al, 2006), 'drilling' tunnels for new vasculature by producing tubular destruction of the matrix and distributing to form columns and capillary-like structures containing erythrocytes (Moldovan et al, 2000), localizing in microvessels embedded in bundles of fibrillar collagen (Anghelina et al, 2006a), adhering to injured vessel walls, thus accelerating the re-endothelization of the vascular barrier (Fujiyama et al, 2003), and assisting lymphangiogenesis in cornea (Maruyama et al, 2007) and kidney (Kerjaschki et al, 2006). Herein we show that macrophages participate directly in neovessel formation in MM, adding new information on the mechanisms of MM neovascularization and microcirculation.…”

Endothelial progenitor cells: Implications for cardiovascular disease

“…Stem cells within the bone marrow usually exist in a quiescent state and specific signals stimulate the stem cells to differentiate and to be mobilized into the systemic circulation. Beside humoral factors such as cytokines (51)(52)(53), hormones (51,53,54), chemokines (37,55), and drugs (56-58), exercise training (ET) has been shown to increase the number of circulating EPCs (8,9,59,60).…”