John Libbey Eurotext

Hématologie

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Circulating endothelial cells: realities and promises for new therapies of angiogenesis Volume 7, issue 1, Janvier - Février 2001

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Inserm U. 506, bâtiment Lavoisier, hôpital Paul-Brousse, 12, avenue Paul-Vaillant-Couturier, 94807 Villejuif cedex.

An increasing number of studies indicates that during development, endothelial and hematopoietic cells derive from a common progenitor named hemangioblast. The existence of such hemangioblasts in adults was recently suggested, as a consequence of the discovery of circulating endothelial progenitor cells (angioblasts) in the peripheral blood. It is likely that these cells have a medullar origin. Different growth factors like VEGF or G-CSF can mobilize these cells into the blood circulation. These cells are functional, because they can be incorporated into the vessels formed in active angiogenic sites. Cell populations enriched in angioblasts could be obtained by sorting blood cells with a combination of different antibodies raised against surface molecules such as CD34, Ac133, Flk-1/KDR, or specific endothelial markers such as VE-cadherin. When cultured, these cells form foci that grow slowly during about two weeks. The cells then acquire a very high proliferative potential, that could be maintained several weeks along. This kinetic of proliferation is different to that observed for endothelial cells from vessels, that display a lower proliferative potential. The physiological role of these angioblasts is still unclear. However, they display functional properties that are very useful for a potential use of these cells for therapeutic purposes in diseases involving angiogenesis. First, experiments performed in animal models show that these cells are able to improve the vascularization of ischemic tissues. Second, recent studies have shown that in the bone marrow of patients with leukaemia, angiogenesis increases. Leukemic cells produce pro-angiogenic factors such as VEGF. The bcr/abl fusion gene is found in the majority of the haematopoietic cells of patients with chronic myeloid leukaemia (CML). This fusion gene was recently detected in the circulating endothelial cells of patients with CML, thus showing that the chromosomal translocation had occurred in medullar hemangioblasts. These observations indicate that medullar angiogenesis may play a role in the proliferation of leukemic cells. Inhibition of this angiogenesis may be a new strategy for the treatment of leukaemia. Finally, experiments performed in monkeys have shown that the circulating angioblasts are accessible for gene transfer. These cells are specifically targeted to the sites of neo-angiogenesis. They are also able to deliver cytotoxic agents locally. Circulating angioblasts thus represent an original and promising tool for gene therapy.