Hypoxic preconditioning reinforces cellular functions of autologous peripheral blood-derived cells in rabbit hindlimb ischemia model.
Hypoxic preconditioning reinforces cellular functions of autologous peripheral blood-derived cells in rabbit hindlimb ischemia model.
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DOI：
10.1016/j.bbrc.2014.01.054
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发表时间：
2014-02
影响因子：
3.1
通讯作者：
T. Kudo;Tohru Hosoyama;M. Samura;S. Katsura;Arata Nishimoto;Naruji Kugimiya;Y. Fujii;Tao-Sheng Li;K. Hamano
中科院分区：
文献类型：
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作者：
T. Kudo;Tohru Hosoyama;M. Samura;S. Katsura;Arata Nishimoto;Naruji Kugimiya;Y. Fujii;Tao-Sheng Li;K. Hamano
外周血单个核细胞（PBMNC）是治疗下肢缺血血管新生的有力工具之一。然而，移植PBMNCs的传统方法对严重缺血患者的治疗效果较差。在这项研究中，我们使用自体移植模型，以确定是否缺氧预处理有效地增强PBMNCs的细胞功能，改善后肢缺血。在低氧条件下培养兔外周血单个核细胞。预处理后，体外检测细胞粘附、抗应激能力和血管生成因子表达。为了检查体内效应，我们在术后第7天将预处理的PBMNCs自体移植到兔后肢缺血模型中。预处理的PBMNCs在抗氧化应激、细胞活力和血管内皮生长因子的产生方面显示出显著增强的功能能力。此外，自体移植预处理的PBMNCs显着诱导新血管和改善肢体血流。重要的是，尽管在POD 7移植，预处理的PBMNCs仍可以加速血管形成，而未处理的PBMNCs血管化较差。我们的研究表明，PBMNCs的低氧预处理是一种可行的方法，以增加移植细胞的保留和促进缺血组织中的治疗性血管生成。
Peripheral blood mononuclear cell (PBMNC) is one of powerful tools for therapeutic angiogenesis in hindlimb ischemia. However, traditional approaches with transplanted PBMNCs show poor therapeutic effects in severe ischemia patients. In this study, we used autograft models to determine whether hypoxic pretreatment effectively enhances the cellular functions of PBMNCs and improves hindlimb ischemia. Rabbit PBMNCs were cultured in the hypoxic condition. After pretreatment, cell adhesion, stress resistance, and expression of angiogenic factor were evaluatedin vitro. To examinein vivoeffects, we autografted preconditioned PBMNCs into a rabbit hindlimb ischemia model on postoperative day (POD) 7. Preconditioned PBMNCs displayed significantly enhanced functional capacities in resistance to oxidative stress, cell viability, and production of vascular endothelial growth factor. In addition, autologous transplantation of preconditioned PBMNCs significantly induced new vessels and improved limb blood flow. Importantly, preconditioned PBMNCs can accelerate vessel formation despite transplantation on POD 7, whereas untreated PBMNCs showed poor vascularization. Our study demonstrated that hypoxic preconditioning of PBMNCs is a feasible approach for increasing the retention of transplanted cells and enhancing therapeutic angiogenesis in ischemic tissue.