Synergistic Neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells - The role of angiogenic cytokines and matrix metalloproteinases
Synergistic Neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells - The role of angiogenic cytokines and matrix metalloproteinases
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DOI：
10.1161/circulationaha.104.503433
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发表时间：
2005-09-13
期刊：
影响因子：
37.8
通讯作者：
Kim, HS
中科院分区：
文献类型：
--
作者：
Yoon, CH;Hur, J;Kim, HS
背景：正如之前报道的，从人外周血中培养出两种类型的细胞，早期内皮祖细胞（EPCs）和生长内皮细胞（OECs）。在这里，我们进一步表征这些细胞，特别是关于它们在体外和体内的不同来源和功能。我们还研究了这些不同细胞类型的组合在新生血管形成过程中是否表现出协同作用。方法和结果-早期EPCs由分泌细胞因子的CD14（+）单核细胞衍生细胞和含有高水平CD34(+)KDR（+）细胞的CD14（-）衍生细胞组成。oec几乎完全来自CD14（-）细胞，而不是CD14（-）细胞，并且在增殖潜力，KDR+表达水平和端粒酶活性方面与成熟内皮细胞不同。来自CD14（-）细胞和早期EPCs的部分细胞在Matrigel塞和缺血后肢中产生快速增殖的毛细血管形成细胞，类似于oec。早期EPCs和oec表达血管内皮生长因子和白细胞介素-8受体，这是早期EPCs分泌的细胞因子。基质金属蛋白酶（MMPs）有不同程度的增加：早期EPCs中有MMP-9， oec中有MMP-2。在体外，两种细胞类型通过细胞因子和MMPs的相互作用增强了血管生成能力。注射这两种细胞的混合物在体内的新生血管形成优于任何单细胞类型的移植。结论：存在不同来源的不同类型的内皮祖细胞，它们在新生血管中具有不同的功能。这些细胞的混合移植通过细胞因子和MMPs产生协同新生血管。
Background - Two types of cells are cultured from the human peripheral blood, early endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs), as previously reported. Here, we further characterize these cells, especially with respect to their different origins and functions both in vitro and in vivo. We also investigated whether the combination of these different cell types shows synergism during neovascularization.Methods and Results - Early EPCs were heterogeneously made up of both CD14(+) monocyte-derived cells, which secrete cytokines, and CD14(-)-derived cells, which contain high levels of CD34(+)KDR(+) cells. OECs were cultured almost exclusively from CD14(-) cells, not CD14(-) cells, and were distinct from mature endothelial cells in terms of proliferation potential, KDR+ expression level, and telomerase activity. A portion of cells from CD14(-) cells and early EPCs produced rapidly proliferating, capillary-forming cells in both the Matrigel plug and the ischemic hind limb similar to OECs. Early EPCs and OECs expressed receptors for vascular endothelial growth factor and interleukin-8, cytokines secreted by early EPCs. There was a differential increase in matrix metalloproteinases ( MMPs): MMP-9 in early EPCs and MMP-2 in OECs. In vitro, the angiogenic capability of the 2 cell types was augmented by mutual interaction through cytokines and MMPs. Injection of a mixture of the 2 cells resulted in superior neovascularization in vivo to any single-cell-type transplantation.Conclusions - Distinct origins of the different types of EPCs exist that have different functions in neovascularization. Mixed transplantation of these cells results in synergistic neovascularization through cytokines and MMPs.