Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels
Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels
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DOI：
10.1182/blood-2005-08-3215
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发表时间：
2006-05-01
期刊：
影响因子：
20.3
通讯作者：
Giacca, M
中科院分区：
文献类型：
--
作者：
Zentilin, L;Taturo, S;Giacca, M
血管内皮生长因子（VEGF）是血管发生和血管生成过程中血管形成的关键调节因子。AAV载体基因转染后，成年啮齿动物正常灌注骨骼肌中VEGF的表达延长，诱导大量新毛细血管和小动脉的形成。值得注意的是，这一过程伴随着单个核细胞的大量浸润。这一观察结果提出了一种可能性，即这些细胞可能代表了最终被合并到新形成的血管中的循环祖细胞。在这里，我们通过利用4种不同的实验模型来探索这种可能性：(a)将男性骨髓移植到女性受体中；(b)转Tie2-GFP的骨髓移植；(c)有促红细胞生成素（EPO）存在的骨髓移植，促红细胞生成素是内皮祖细胞（EPCs）的动员剂；(d)体外扩增EPCs的再植。在所有4种模型中，VEGF都是骨髓来源的单个核细胞的强大吸引剂，在新生血管形成的部位携带不同的内皮细胞的髓系和内皮标记物。然而，在任何情况下，被吸引的细胞都不会被纳入新形成的脉管系统。这些观察结果表明，VEGF诱导的新血管形成是通过真正的发芽血管生成发生的；浸润性骨髓源性细胞在这一过程中的作用仍然是个谜。
Vascular endothelial growth factor (VEGF) is a key regulator of blood vessel formation during both vasculogenesis and angiogenesis. The prolonged expression of VEGF in the normoperfused skeletal muscles of adult rodents after gene transfer using AAV vectors induces the formation of a large set of new capillaries and small arteries. Notably, this process is accompanied by the massive Infiltration by mononuclear cells. This observation raises the possibility that these cells might represent circulating progenitors that are eventually incorporated in the newly formed vessels. Here we explore this possibility by exploiting 4 different experimental models based on (a) the transplantation of male bone marrow into female recipients; (b) the transplantation of Tie2-GFP transgenic bone marrow; (c) the transplantation of bone marrow in the presence of erythropoietin (EPO), a mobilizer of endothelial progenitor cells (EPCs); and (d) the reimplantation of ex vivo-expanded EPCs. In all 4 models, VEGF acted as a powerful attractor of bone marrow-derived mononuclear cells, bearing different myeloid and endothelial markers proper of the EPCs to the sites of neovascularization. In no case, however, were the attracted cells incorporated in the newly formed vasculature. These observations indicate that new blood vessel formation induced by VEGF occurs through bona fide sprouting angiogenesis; the contribution of the infiltrating bone marrow-derived cells to this process still remains enigmatic.