Hypoxic preconditioning increases survival and angiogenic potency of peripheral blood mononuclear cells via oxidative stress resistance
Hypoxic preconditioning increases survival and angiogenic potency of peripheral blood mononuclear cells via oxidative stress resistance
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DOI：
10.1152/ajpheart.00856.2007
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发表时间：
2008-02-01
影响因子：
4.8
通讯作者：
Hamano, Kimikazu
中科院分区：
文献类型：
--
作者：
Kubo, Masayuki;Li, Tao-Sheng;Hamano, Kimikazu
基于细胞的血管生成是缺血性疾病的一种有前途的治疗方法;然而，植入细胞的存活受到缺血微环境中氧化应激的损害。我们测试了植入细胞的低氧预处理增强其对氧化应激的抵抗力，增加植入缺血组织后的细胞存活率和血管生成能力的假设。收集小鼠外周血单个核细胞（PBMNCs），在33 ℃、2%O-2中培养24 h，进行低氧预处理。低氧预处理可显著增加PBMNCs抗氧化和生存信号相关基因的表达。与常氧条件下培养的细胞相比，低氧预处理的PBMNCs在LY-83583（一种超氧化物发生剂）诱导的氧化应激下表现出显著降低的活性氧（ROS）积累和较高的细胞存活率。肌内植入小鼠缺血后肢3天后，低氧预处理的PBMNCs的存活率较高，而常氧培养的PBMNCs的存活率相对较低。此外，治疗28天后，植入缺氧预处理PBMNCs的小鼠缺血后肢的微血管密度和血流量明显好于植入常氧培养PBMNCs的小鼠。低氧预处理通过抗氧化应激机制增加PBMNCs的存活和血管生成能力。
Cell-based angiogenesis is a promising treatment for ischemic diseases; however, the survival of implanted cells is impaired by oxidative stress in the ischemic microenvironment. We tested the hypothesis that hypoxic preconditioning of implanted cells enhances their resistance against oxidative stress, increasing cell survival and angiogenic potency after implantation into ischemic tissue. Mouse peripheral blood mononuclear cells (PBMNCs) were collected and subjected to hypoxic preconditioning by culture for 24 h in 2% O-2 at 33 C. Hypoxic preconditioning of PBMNCs increased the expression of various genes related to antioxidant and survival signals remarkably. Compared with cells cultured under normoxia, the hypoxia-preconditioned PBMNCs showed significantly lower reactive oxygen species (ROS) accumulation and higher cell survival under oxidative stress induced by LY-83583 (a superoxide generator). Three days after intramuscular implantation into the ischemic hindlimbs of mice, survival of the hypoxia-preconditioned PBMNCs was high, whereas that of the normoxia-cultured PBMNCs was relatively low. Furthermore, 28 days after treatment microvessel density and blood flow in the ischemic hindlimbs were significantly better in the mice implanted with hypoxia-preconditioned PBMNCs than in those implanted with normoxia-cultured PBMNCs. Hypoxic preconditioning increased the survival and angiogenic potency of PBMNCs, through oxidative stress resistance mechanisms.