Although cord blood (CB) offers promise for treatment of patients with high-risk hematological malignancies and immune disorders, the limited numbers of hematopoietic stem cell (HSC)/progenitor cell in a CB unit and straitened circumstances in expanding ex vivo make it quite challenging to develop the successful cell therapies. In this study, a novel strategy has been developed to support ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) by coculture with engineered human umbilical arterial endothelial cells (HuAECs-E4orf1-GFP), which expresses E4ORF1 stably by using a retroviral system. Coculture of CD34+ hCB cells with HuAECs-E4orf1-GFP resulted in generation of considerably more total nucleated cells, CD34+CD38−, and CD34+CD38−CD90+ HSPCs in comparison with that of cytokines alone or that of coculture with human umbilical vein endothelial cells (HuVECs) after 14-day amplification. The in vitro multilineage differentiation potential and in vivo repopulating capacity of the expanded hematopoietic cells cocultured with HuAECs-E4orf1-GFP were also markedly enhanced compared with the other two control groups. DLL4, a major determinant of arterial endothelial cell (EC) identity, was associated with CD34+ hCB cells amplified on HuAECs-E4orf1-GFP. Collectively, we demonstrated that HuAECs acted as a permissive niche in facilitating expansion of HSPCs. Our study further implicated that the crucial factors and related pathways presented in HuAECs may give a hint to maintain self-renewal of bona fide HSCs.

中文翻译：

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动脉内皮为人类脐带血造血干细胞和祖细胞的扩增创造了一个合适的环境。

尽管脐带血（CB）为治疗高危血液系统恶性肿瘤和免疫疾病的患者提供了希望，但CB单位中造血干细胞（HSC）/祖细胞的数量有限以及离体扩大的局限性环境使其颇具挑战性发展成功的细胞疗法。在这项研究中，已开发出一种新的策略来支持通过与工程化的人脐动脉内皮细胞（HuAECs-E4orf1-GFP）共培养来支持造血干细胞和祖细胞（HSPC）的离体扩增，后者通过使用逆转录病毒系统稳定表达E4ORF1 。CD34 + hCB细胞与HuAECs-E4orf1-GFP的共培养导致产生了更多的总有核细胞，即CD34 + CD38-，和CD34 + CD38-CD90 + HSPC与单独的细胞因子相比，或与人脐静脉内皮细胞（HuVEC）共培养14天后的细胞因子比较。与其他两个对照组相比，与HuAECs-E4orf1-GFP共培养的扩增的造血细胞的体外多系分化潜能和体内再繁殖能力也显着增强。DLL4是动脉内皮细胞（EC）身份的主要决定因素，与在HuAECs-E4orf1-GFP上扩增的CD34 + hCB细胞相关。总体而言，我们证明了HuAEC在促进HSPC扩展方面发挥了一定的利基作用。我们的研究进一步暗示，HuAECs中提出的关键因素和相关途径可能为维持真正的HSC自我更新提供暗示。与其他两个对照组相比，与HuAECs-E4orf1-GFP共培养的扩增的造血细胞的体外多系分化潜能和体内再繁殖能力也显着增强。DLL4是动脉内皮细胞（EC）身份的主要决定因素，与在HuAECs-E4orf1-GFP上扩增的CD34 + hCB细胞相关。总体而言，我们证明了HuAEC在促进HSPC扩展方面发挥了一定的利基作用。我们的研究进一步暗示，HuAECs中提出的关键因素和相关途径可能为保持真正的HSC自我更新提供暗示。与其他两个对照组相比，与HuAECs-E4orf1-GFP共培养的扩增的造血细胞的体外多系分化潜能和体内再繁殖能力也显着增强。DLL4是动脉内皮细胞（EC）身份的主要决定因素，与在HuAECs-E4orf1-GFP上扩增的CD34 + hCB细胞相关。总体而言，我们证明了HuAEC在促进HSPC扩展方面发挥了一定的利基作用。我们的研究进一步暗示，HuAECs中提出的关键因素和相关途径可能为维持真正的HSC自我更新提供暗示。动脉内皮细胞（EC）身份的主要决定因素与在HuAECs-E4orf1-GFP上扩增的CD34 + hCB细胞有关。总体而言，我们证明了HuAEC在促进HSPC扩展方面发挥了一定的利基作用。我们的研究进一步暗示，HuAECs中提出的关键因素和相关途径可能为维持真正的HSC自我更新提供暗示。动脉内皮细胞（EC）身份的主要决定因素与在HuAECs-E4orf1-GFP上扩增的CD34 + hCB细胞有关。总体而言，我们证明了HuAEC在促进HSPC扩展方面发挥了一定的利基作用。我们的研究进一步暗示，HuAECs中提出的关键因素和相关途径可能为维持真正的HSC自我更新提供暗示。