The Laboratory for Lymphocyte Biology, Department of Biomedicine, Aarhus University, Aarhus, Denmark.
PLoS One. 2021 Mar 17;16(3):e0247501. doi: 10.1371/journal.pone.0247501. eCollection 2021.
Murine bone marrow (BM) chimeras are a versatile and valuable research tool in stem cell and immunology research. Engraftment of donor BM requires myeloablative conditioning of recipients. The most common method used for mice is ionizing radiation, and Cesium-137 gamma irradiators have been preferred. However, radioactive sources are being out-phased worldwide due to safety concerns, and are most commonly replaced by X-ray sources, creating a need to compare these sources regarding efficiency and potential side effects. Prior research has proven both methods capable of efficiently ablating BM cells and splenocytes in mice, but with moderate differences in resultant donor chimerism across tissues. Here, we compared Cesium-137 to 350 keV X-ray irradiation with respect to immune reconstitution, assaying complete, syngeneic BM chimeras and a mixed chimera model of autoimmune disease. Based on dose titration, we find that both gamma and X-ray irradiation can facilitate a near-complete donor chimerism. Mice subjected to 13 Gy Cesium-137 irradiation and reconstituted with syngeneic donor marrow were viable and displayed high donor chimerism, whereas X-ray irradiated mice all succumbed at 13 Gy. However, a similar degree of chimerism as that obtained following 13 Gy gamma irradiation could be achieved by 11 Gy X-ray irradiation, about 85% relative to the gamma dose. In the mixed chimera model of autoimmune disease, we found that a similar autoimmune phenotype could be achieved irrespective of irradiation source used. It is thus possible to compare data generated, regardless of the irradiation source, but every setup and application likely needs individual optimization.
鼠骨髓（BM）嵌合体是干细胞和免疫学研究中一种多功能且有价值的研究工具。供体 BM 的植入需要对受者进行骨髓清除性调理。最常用于小鼠的方法是电离辐射，铯-137 γ辐照器是首选。然而，由于安全问题，放射性源在全球范围内正在被淘汰，并且最常用 X 射线源替代，因此需要比较这些源的效率和潜在副作用。先前的研究已经证明，这两种方法都能够有效地清除小鼠的 BM 细胞和脾细胞，但在组织中的供体嵌合体的结果存在适度差异。在这里，我们比较了铯-137 与 350 keV X 射线照射在免疫重建方面的差异，检测了完全同基因 BM 嵌合体和自身免疫疾病的混合嵌合体模型。根据剂量滴定，我们发现γ和 X 射线照射都可以促进近乎完全的供体嵌合体。接受 13 Gy 铯-137 照射并用同基因供体骨髓重建的小鼠是存活的，并显示出高供体嵌合体，而接受 X 射线照射的小鼠在 13 Gy 时全部死亡。然而，通过 11 Gy X 射线照射可以实现与 13 Gy γ照射获得的相似程度的嵌合体，相对于 γ剂量约为 85%。在自身免疫疾病的混合嵌合体模型中，我们发现无论使用何种辐射源，都可以获得相似的自身免疫表型。因此，无论使用何种辐射源，都可以比较生成的数据，但每个设置和应用可能都需要单独的优化。
