The fetal mouse metatarsal bone explant as a model of angiogenesis
Weihua SongChee Wai FhuKoon Hwee AngChenghao LiuNurul Azizah Binte JohariDaniel Chin Shiuan LioSabu AbrahamWanjin HongStephen E. MossJohn GreenwoodXiaomeng Wang
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A bstract : Postnatal neovascularization has previously been considered synonymous with angiogenesis, but the finding that circulating endothelial progenitor cells (EPCs) may home to sites of neovascularization and there differentiate into endothelial cells (ECs) is consistent with “vasculogenesis,” through which the primordial vascular network is established in the embryo. Our findings suggest that growth and development of new blood vessels in the adult are not restricted to angiogenesis but encompass vasculogenesis as well, although the proportional contributions remain to be clarified. Likewise, augmented or retarded neovascularization probably involves enhancement or impariment of the vasculogenesis process.
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Making Split Decisions Development of the vertebrate vasculature has been thought to involve just two mechanisms of blood vessel formation. Herbert et al. (p. 294 ; see the Perspective by Benedito and Adams ) identified a third mechanism in zebrafish in which two distinct, unconnected vessels can be derived from a single precursor vessel. Several vascular endothelial growth factors and signaling pathways, including ephrin and notch signaling, coordinated the sorting and segregation of a mixture of arterial and venous-fated precursor cells into distinct arterial and venous vessels. These findings provide a mechanistic framework for how mixed populations of cells can coordinate their behavior to segregate and form distinct blood vessels.
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In the embryo, blood vessel formation de novo (vasculogenesis) and from existing vessels (angiogenesis) results in blood vessels lined by endothelial cells (ECs). The relationship between ECs and blood cells suggested by their physical closeness was recently confirmed with the demonstration of progenitors that give rise to both cell types. In tumors, new blood vessel formation has been thought to occur primarily via angiogenesis. Recent evidence, however, suggests that postnatal vasculogenesis also contributes to tumor neovascularization. In this article, we provide an update on EC development, including early lineage specification, morphogenesis or differentiation to form functional blood vessels, and regulation of EC survival and senescence. Furthermore, we review the latest findings on tumor neovascularization and therapeutic potentials of molecules critical to this process.
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The formation of new blood vessels from existing blood vessels has been referred to as angiogenesis to distinguish the process from de novo embryonic vessel formation or vasculogenesis (1). This chapter will describe an in vivo assay to measure angiogenesis. There are several important reasons to study and measure angiogenesis in vascular disease. First, it is necessary to try to understand proliferative angiogenesis as it occurs in tumors and in diabetic complications and devise strategies to inhibit it. Second, there is intense interest in improving angiogenesis after ischemia or in chronic wounds (2). Third, many potential modulators of angiogenesis need to be evaluated to determine their effects on blood vessel development.
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In the past decade, researchers have defined committed stem or progenitor cells from various tissues, including bone marrow, peripheral blood, brain, liver and reproductive organs, in both adult animals and humans. Recently, endothelial progenitor cells (EPCs) were isolated from peripheral blood mononuclear cells and were shown to be incorporated into foci of neovascularization. This finding that circulating EPCs may home into sites of neovascularization and differentiate into mature endothelial cells in situ is consistent with the concept of 'vasculogenesis' and suggests that vasculogenesis and angiogenesis might constitute complementary mechanisms for postnatal neovascularization. Furthermore, experimental and clinical studies on ischemic cardiovascular diseases suggest a therapeutic potential for EPC transplantation. In this review, we summarize the biological features of EPCs and discuss their therapeutic potential for the treatment of cardiovascular diseases.
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Peripheral blood of adult species contains endothelial progenitor cells (EPCs) that participate in neovascularization, consistent with postnatal vasculogenesis. EPCs can be isolated not only from peripheral blood but also from bone marrow and human umbilical cord blood. In vitro culture-expanded EPCs participate in endothelial network formation (capillary formation) in vitro, and transplanted EPCs have been incorporated into sites of active neovascularization. For example, transplanted human EPCs formed capillaries among preserved skeletal myocytes in the ischemic hindlimb of athymic nude rats in vivo. Furthermore, transplantation of EPCs functionally augmented neovascularization in response to hindlimb ischemia. Thus, transplantation of EPCs may become a useful strategy to modulate postnatal neovascularization.
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