In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals
In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals
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DOI：
10.1007/s00259-005-0048-4
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发表时间：
2006-05-01
影响因子：
9.1
通讯作者：
Ohtomo, K
中科院分区：
文献类型：
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作者：
Inoue, Y;Tojo, A;Ohtomo, K
目的：体内生物发光成像应用于肿瘤模型的非侵入性定量监测依赖于生物发光强度与肿瘤负荷之间的正相关性。我们进行了细胞培养研究，以探讨生物发光信号强度和活细胞数之间的关系，在小鼠白血病模型cells.Methods：白细胞介素-3（IL-3）依赖的小鼠前B细胞系Ba/F3转导萤火虫荧光素酶产生的细胞稳定表达荧光素酶的逆转录病毒长末端重复序列的控制下。用p190 BCR-ABL转导表达端粒酶的细胞，以产生因子非依赖性增殖。结果：Ba/F3细胞经荧光素酶和p190 BCR-ABL转导后，表现出自主生长和稳定的荧光素酶表达，体内生物发光成像可从体外检测到这些细胞植入小鼠体内。在细胞培养研究中，生物发光强度倾向于反映细胞增殖和对伊马替尼的反应。然而，每个活细胞的发光受到因子依赖性细胞中IL-3浓度和因子非依赖性细胞中增殖阶段和伊马替尼浓度的影响，从而损害活细胞数和生物发光信号强度之间的比例。每个细胞的发光倾向于变化与增殖cells.Conclusion的分数：虽然在体内生物发光成像将允许非侵入性监测白血病模型动物，环境因素和治疗干预可能会导致肿瘤负荷和生物发光强度之间的一些差异。
Purpose: The application of in vivo bioluminescence imaging to non-invasive, quantitative monitoring of tumour models relies on a positive correlation between the intensity of bioluminescence and the tumour burden. We conducted cell culture studies to investigate the relationship between bioluminescent signal intensity and viable cell numbers in murine leukaemia model cells.Methods: Interleukin-3 (IL-3)-dependent murine pro-B cell line Ba/F3 was transduced with firefly luciferase to generate cells expressing luciferase stably under the control of a retroviral long terminal repeat. The luciferase-expressing cells were transduced with p190 BCR-ABL to give factor-independent proliferation. The cells were cultured under various conditions, and bioluminescent signal intensity was compared with viable cell numbers and the cell cycle stage.Results: The Ba/F3 cells showed autonomous growth as well as stable luciferase expression following transduction with both luciferase and p190 BCR-ABL, and in vivo bioluminescence imaging permitted external detection of these cells implanted into mice. The bioluminescence intensities tended to reflect cell proliferation and responses to imatinib in cell culture studies. However, the luminescence per viable cell was influenced by the IL-3 concentration in factor-dependent cells and by the stage of proliferation and imatinib concentration in factor-independent cells, thereby impairing the proportionality between viable cell number and bioluminescent signal intensity. Luminescence per cell tended to vary in association with the fraction of proliferating cells.Conclusion: Although in vivo bioluminescence imaging would allow non-invasive monitoring of leukaemia model animals, environmental factors and therapeutic interventions may cause some discrepancies between tumour burden and bioluminescence intensity.