Cytokines and Matrix Metalloproteinases Progenitor Cells and Late Outgrowth Endothelial Cells: the Role of Angiogenic Synergistic Neovascularization by Mixed Transplantation of Early Endothelial Synergistic Neovascularization by Mixed Transplantation of E-猫眼课题宝

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Han-Kwang Yang;B. Oh;Young‐Bae Park;Hyo‐Soo Kim;I. Oh;Tae-Youn Kim;Hyun-Jai Cho;Hyun-Jae Kang

背景——如先前报道，从人外周血中培养出两种类型的细胞，即早期内皮祖细胞 (EPC) 和生长内皮细胞 (OEC)。在这里，我们进一步表征了这些细胞，特别是它们在体外和体内的不同起源和功能。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 EPC 由 CD14 ϩ 单核细胞衍生的细胞（分泌细胞因子）和 CD14 Ϫ 衍生的细胞（含有高水平的 CD34 ϩ KDR ϩ 细胞）异质组成。 OEC 几乎完全由 CD14 Ϫ 细胞而非 CD14 ϩ 细胞培养而成，并且在增殖潜力、KDR ϩ 表达水平和端粒酶活性方面与成熟内皮细胞不同。来自 CD14Ϫ 细胞和早期 EPC 的一部分细胞在基质胶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 EPC 和 OEC 表达血管内皮生长因子和白细胞介素 8（早期 EPC 分泌的细胞因子）的受体。基质金属蛋白酶 (MMP) 存在差异性增加：早期 EPC 中的 MMP-9 和 OEC 中的 MMP-2。在体外，两种细胞类型的血管生成能力通过细胞因子和基质金属蛋白酶的相互作用而增强。注射两种细胞的混合物导致体内新血管形成优于任何单细胞类型的移植。结论——不同类型的 EPC 存在不同的起源，它们在新生血管形成中具有不同的功能。这些细胞的混合移植通过细胞因子和基质金属蛋白酶导致协同新血管形成。

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 ϩ monocyte-derived cells, which secrete cytokines, and CD14 Ϫ-derived cells, which contain high levels of CD34 ϩ KDR ϩ cells. OECs were cultured almost exclusively from CD14 Ϫ cells, not CD14 ϩ cells, and were distinct from mature endothelial cells in terms of proliferation potential, KDR ϩ expression level, and telomerase activity. A portion of cells from CD14 Ϫ 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.

Cytokines and Matrix Metalloproteinases Progenitor Cells and Late Outgrowth Endothelial Cells: the Role of Angiogenic Synergistic Neovascularization by Mixed Transplantation of Early Endothelial Synergistic Neovascularization by Mixed Transplantation of E

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