Induction of Embryonic Vasculogenesis by bFGF and LIFin Vitroandin Vivo

Abstract

The de novo formation of blood vessels (vasculogenesis) is an integral part of embryogenesis. Elucidation of the role of cytokine cooperation in vasculogenesis may lead to a better understanding of organogenesis, blood vessel regulation during tumorigenesis, and tissue injury. We have used embryonic stem cells to derive an endothelial cell line, designated IEM, which expresses a range of endothelial markers, including Von Willibrand Factor VIII related antigen, vascular cell adhesion molecule, platelet-endothelial cell adhesion molecule (CD31), and receptors for acetylated low-density lipoprotein. More importantly, IEM cells can be induced upon exposure to combinations of basic fibroblast growth factor and leukemia inhibitory factor (LIF) to proliferate and undergo vasculogenesis in vitro, resulting in the formation of vascular tubes and microcapillary anastomoses. Moreover, exposure to both cytokines conditionally permits IEM cells to specifically chimerize microvascular endothelium in vivo following blastocyst injection. These results indicate that bFGF and LIF together contribute to the induction and support of embryonic vasculogenesis in an isolated endothelial cell line. Our results provide evidence that combined actions of bFGF/LIF may play a role in mechanisms controlling blood vessel development.

Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma

“…VEGFR-1 mediates macrophage chemotaxis (Barleon et al, 1996) and the organization of the embryo vasculature by vasculogenesis (Fong et al, 1995), but not the definitive vessel assembly, which is closely dependent on VEGFR-2, a specific EC differentiation marker (Shalaby et al, 1999). The bFGF/ FGFRs system is mandatory for vasculogenesis, since it induces angioblasts to differentiate and assemble into initial vascular patterns (Gendron et al, 1996).…”

Exogenous leukemia inhibitory factor (LIF) attenuates retinal vascularization reducing cell proliferation not apoptosis

“…It has been shown to cause proliferation (Gendron et al, 1996) and induce tube-formation (Paradis and Gendron, 2000) of an embryonic endothelial cell line. However, it had differential effects on bovine endothelial cells depending on the tissue origin of the cells.…”

Immunolocalisation of leukaemia inhibitory factor in the cornea

“…Although factors such as VEGF, which modulates cornea, and new vascularisation has been characterised, the process of vascularisation is far from clear. Several studies have indicated that LIF could play a role in the regulation of blood vessel formation, [25][26][27][28][29] and LIF may have an implication in pathological vascularisation in ocular tissues. Depending upon the tissue origin or stage of differentiation, LIF has been shown to exert different actions.…”

“…LIF stimulates adrenal cortex endothelial cells and embryonic cells, while it inhibit aortic endothelial cells. [25][26][27] Embryonic endothelial cell line can be optimally induced to differentiate into capillary-like structures in vitro by combined exposure to LIF plus bFGF. 26,28 During the formation of capillary structures from embryonic endothelial cell, line twoFStat3 and P 41/43MAPK cascade systems are activated.…”

“…[25][26][27] Embryonic endothelial cell line can be optimally induced to differentiate into capillary-like structures in vitro by combined exposure to LIF plus bFGF. 26,28 During the formation of capillary structures from embryonic endothelial cell, line twoFStat3 and P 41/43MAPK cascade systems are activated. 29 Stat3 acts as negative regulators on capillary development, and inhibition of this pathway is accompanied by increases capillary outgrowth, while inhibition of P 41/43MAPK pathway dramatically reduces the capillary formation.…”