Role of oxidative stress in hypoxia preconditioning of cells transplanted to the myocardium: a molecular imaging study.
Role of oxidative stress in hypoxia preconditioning of cells transplanted to the myocardium: a molecular imaging study.
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发表时间：
2011-08
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通讯作者：
A. Aly;K. Peterson;A. Lerman;L. Lerman;M. Rodriguez-Porcel
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作者：
A. Aly;K. Peterson;A. Lerman;L. Lerman;M. Rodriguez-Porcel
目的细胞疗法是治疗冠状动脉疾病的一种潜在的治疗方法。然而，移植的细胞在活的受试者中经历显著死亡。低氧预处理（HPC）是一种潜在的干预措施，以增加移植细胞的存活。然而，这种益处的生物学机制仍不清楚。我们假设HPC对干细胞存活的有益作用部分是由于氧化状态的保持，这种作用将使用最先进的分子成像进行监测。方法将表达CMV-萤火虫荧光素酶（h9 c2-fluc）的H9 c2大鼠心肌细胞暴露于缺氧条件下，检测氧化应激和细胞存活率。随后，H9 c2-fluc细胞，有和没有HPC，被注射到大鼠的心肌和细胞存活进行了监测，每天与生物发光（BLI）使用CCD相机。结果与对照组相比，缺氧暴露的细胞活性氧增加（ROS，对照组：14.1±0.9 vs.缺氧：19.5 ± 2.0 RFU/µg protein，P=0.02），细胞存活率降低（对照组：0.29 ± 0.005 vs.缺氧：0.24 ± 0.005 OD，P<0.001）。HPC处理降低了缺氧诱导的ROS量（HPC：11.5 ± 0.7RFU/µg蛋白，与缺氧相比P=0.002，与对照相比P=0.11），与生存率改善相关（HPC：0.27 ± 0.004OD/µg蛋白，与缺氧相比P=0.002，与对照相比P=0.005）。最重要的是，与未调节的细胞相比，HPC细胞在移植到心肌后具有增加的细胞存活率（C：34.7 ± 6.7% vs. HPC：83.4 ± 17.5%，第5天与第1天相比，P=0.01）。结论HPC的有益作用部分是由于其保持了机体的氧化状态。分子成像可以评估活体受试者中细胞存活的变化，并具有临床应用的潜力。
AIM Cell-based therapies are a potential therapeutic alternative for the treatment of coronary artery disease (CAD). However, transplanted cells undergo significant death in the living subject. Hypoxic preconditioning (HPC) is a potential intervention to increase transplanted cell survival. However, the biological mechanisms of this benefit remain unclear. We hypothesize that the beneficial effect of HPC on stem cell survival is in part due to preservation of oxidant status, an effect that will be monitored using state-of-the-art molecular imaging. METHODS H9c2 rat cardiomyoblasts expressing the construct CMV-firefly luciferase (h9c2-fluc), with and without HPC, were exposed to hypoxia, and oxidative stress and cell survival were measured. Subsequently, H9c2-fluc cells, with and without HPC, were injected into the myocardium of rats and cell survival was monitored daily with Bioluminescence (BLI) using a CCD camera. RESULTS Compared to controls, cells exposed to hypoxia had increased amount of reactive oxygen species (ROS, control: 14.1±0.9 vs. hypoxia: 19.5 ± 2.0 RFU/µg protein, P=0.02) and decreased cell survival (control: 0.29 ± 0.005 vs. hypoxia: 0.24 ± 0.005 OD, P<0.001). HPC treatment decreased the amount of hypoxia-induced ROS (HPC: 11.5 ± 0.7RFU/µg protein, P=0.002 vs. hypoxia and P=0.11 vs. control), associated with improved survival (HPC: 0.27 ± 0.004OD/µg protein, P=0.002 vs. hypoxia and P=0.005 vs. control). Most importantly, compared to un-conditioned cells, HPC-cells had increased cell survival after transplantation to the myocardium (C: 34.7 ± 6.7% vs. HPC: 83.4 ± 17.5% at day 5 compared to day 1, P=0.01). CONCLUSION The beneficial effect of HPC is in part due to preservation of oxidant status. Molecular imaging can assess changes in cell survival in the living subject and has the potential to be applied clinically.