Endothelial differentiation potential of human monocyte-derived multipotential cells
Endothelial differentiation potential of human monocyte-derived multipotential cells
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DOI：
10.1634/stemcells.2006-0026
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发表时间：
2006-12-01
期刊：
影响因子：
5.2
通讯作者：
Ikeda, Yasuo
中科院分区：
文献类型：
--
作者：
Kuwana, Masataka;Okazaki, Yuka;Ikeda, Yasuo
我们以前报道了一种独特的CD 14（+）CD 45（+）CD 34（+）I型胶原（+）细胞组分，来源于人循环中的CD 14（+）单核细胞，称为单核细胞衍生的多能细胞（MOMCs）。这种原始细胞群含有能够沿着间充质和神经元谱系分化的祖细胞。在这里，我们研究了MOMCs是否也可以沿着内皮细胞系沿着分化。用血管生成生长因子处理7天的MOMCs在形态上发生变化，并采用尾状外观，具有类似于韦伯-帕拉德体的杆状微管结构。几乎每个细胞都表达CD 31、CD 144、血管内皮生长因子（VEGF）1型和2型受体、Tie-2、血管性血友病因子（vWF）、内皮一氧化氮合酶和CD 146，但CD 14/CD 45表达显著下调。在这些培养条件下，MOMC继续增殖长达7天。功能特征，包括组胺刺激后vWF释放和VEGF和VEGF 1型受体表达上调，在缺氧反应，是无法区分的MOMC衍生的内皮样细胞和培养的成熟内皮细胞。MOMCs对血管生成刺激作出反应，并促进Matrigel培养物中成熟内皮细胞小管的形成。最后，在使用严重联合免疫缺陷小鼠模型的异种移植研究中，皮下注射有或没有人MOMC的同基因结肠癌细胞。MOMCs的共移植促进了血管的形成，超过40%的肿瘤血管切片掺入了来自MOMCs的人内皮细胞。这些发现表明，人MOMCs可以增殖和分化沿着内皮细胞谱系在一个特定的许可的环境，因此代表了自体移植的细胞来源治疗性新生血管。
We previously reported a unique CD14(+)CD45(+)CD34(+) type I collagen(+) cell fraction derived from human circulating CD14(+) monocytes, named monocyte-derived multipotential cells (MOMCs). This primitive cell population contains progenitors capable of differentiating along the mesenchymal and neuronal lineages. Here, we investigated whether MOMCs can also differentiate along the endothelial lineage. MOMCs treated with angiogenic growth factors for 7 days changed morphologically and adopted a caudate appearance with rod-shaped microtubulated structures resembling Weibel-Palade bodies. Almost every cell expressed CD31, CD144, vascular endothelial growth factor ( VEGF) type 1 and 2 receptors, Tie-2, von Willebrand factor (vWF), endothelial nitric-oxide synthase, and CD146, but CD14/CD45 expression was markedly downregulated. Under these culture conditions, the MOMCs continued to proliferate for up to 7 days. Functional characteristics, including vWF release upon histamine stimulation and upregulated expression of VEGF and VEGF type 1 receptor in response to hypoxia, were indistinguishable between the MOMC-derived endothelial-like cells and cultured mature endothelial cells. The MOMCs responded to angiogenic stimuli and promoted the formation of mature endothelial cell tubules in Matrigel cultures. Finally, in xenogenic transplantation studies using a severe combined immunodeficient mouse model, syngeneic colon carcinoma cells were injected subcutaneously with or without human MOMCs. Cotransplantation of the MOMCs promoted the formation of blood vessels, and more than 40% of the tumor vessel sections incorporated human endothelial cells derived from MOMCs. These findings indicate that human MOMCs can proliferate and differentiate along the endothelial lineage in a specific permissive environment and thus represent an autologous transplantable cell source for therapeutic neovasculogenesis.