Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
PLoS One. 2020 Oct 29;15(10):e0241375. doi: 10.1371/journal.pone.0241375. eCollection 2020.
Humanized mouse models are used extensively in research involving human pathogens and diseases. However, most of these models require preconditioning. Radio-active sources have been used routinely for this purpose but safety issues have motivated researchers to transition to chemical or X-ray based preconditioning. In this study, we directly compare 350 kV X-ray and Cs-137 low-dose precondition of NOG mice before human stem cell transplantation. Based on flow cytometry data, we found that engraftment of human cells into the mouse bone marrow was similar between radiation sources. Likewise, human engraftment in the peripheral blood was comparable between Cs-137 and three different X-ray doses with equal chimerization kinetics. In primary lymphoid organs such as the thymus and lymph nodes, and spleen, liver and lung, human-to-mouse chimerization was also comparable between irradiation sources. Development of different CD4 and CD8 T cells as well as these cells' maturation stages, i.e. from naïve to effector and memory subsets were generally analogous. Based on our results, we conclude that there are no discernable differences between the two sources in the low-dose spectrum investigated. However, while we encourage the transition to X-ray-based sources, we recommend all research groups to consider technical specifications and dose-finding studies.
人源化小鼠模型广泛应用于涉及人类病原体和疾病的研究。然而，这些模型大多需要预处理。为此，放射性源已被常规使用，但出于安全考虑，研究人员已转而使用化学或 X 射线预处理。在这项研究中，我们在进行人干细胞移植前，直接比较了 350kV X 射线和 Cs-137 低剂量预处理的 NOG 小鼠。基于流式细胞术数据，我们发现两种辐射源的人细胞在骨髓中的植入情况相似。同样，Cs-137 和三种不同 X 射线剂量之间的人细胞外周血植入情况也相似，嵌合动力学相当。在初级淋巴器官（如胸腺、淋巴结和脾脏）以及肝脏和肺部，两种辐射源之间的人-鼠嵌合情况也相似。不同的 CD4 和 CD8 T 细胞的发育以及这些细胞的成熟阶段，即从幼稚到效应和记忆亚群，通常是类似的。根据我们的结果，我们得出结论，在所研究的低剂量范围内，两种来源之间没有明显差异。然而，尽管我们鼓励转向基于 X 射线的来源，但我们建议所有研究小组考虑技术规格和剂量探索研究。
