Myeloid Engraftment in Humanized Mice: Impact of Granulocyte-Colony Stimulating Factor Treatment and Transgenic Mouse Strain
Myeloid Engraftment in Humanized Mice: Impact of Granulocyte-Colony Stimulating Factor Treatment and Transgenic Mouse Strain
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DOI：
10.1089/scd.2015.0289
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发表时间：
2016-04-01
影响因子：
4
通讯作者：
Little, Mark A.
中科院分区：
文献类型：
--
作者：
Coughlan, Alice M.;Harmon, Cathal;Little, Mark A.
骨髓移植不良仍然是人源化小鼠实验应用的一个障碍。主要以外周血细胞为研究对象，我们比较了NOD-scid-IL2R γ c(-/-) （NSG）小鼠与转人膜干细胞因子（hu-mSCF小鼠）、转人白细胞介素(IL)-3、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和干细胞因子（SGM3小鼠）的移植情况。与NSG小鼠相比，hu-mSCF和SGM3小鼠的人白细胞植入量增加，这反映在这些菌株中存在的人中性粒细胞和单核细胞数量上。重要的是，在NSG和hu-mSCF小鼠的血液中可以识别出离散的经典、中间和非经典单核细胞群体，而在SGM3小鼠的血液中没有非经典群体。粒细胞集落刺激因子（GCSF）处理增加了NSG和- mscf小鼠的血液单核细胞数量，增加了NSG和SGM3小鼠的中性粒细胞数量；然而，这种效果似乎至少部分依赖于用于移植小鼠的干细胞供体。此外，GCSF处理导致NSG和hu-mSCF小鼠的非经典单核细胞优先扩增。人小管间质CD11c（+）细胞存在于hu-mSCF小鼠的肾脏中，而在所有菌株的肝脏中均鉴定出单核细胞和中性粒细胞。NSG小鼠骨髓源性巨噬细胞对聚苯乙烯珠粒的吞噬效果最好。综上所述，hu-mSCF小鼠为人髓细胞的产生提供了最佳的环境，GCSF处理进一步提高了该菌株外周血人单核细胞的数量。
Poor myeloid engraftment remains a barrier to experimental use of humanized mice. Focusing primarily on peripheral blood cells, we compared the engraftment profile of NOD-scid-IL2R gamma c(-/-) (NSG) mice with that of NSG mice transgenic for human membrane stem cell factor (hu-mSCF mice), NSG mice transgenic for human interleukin (IL)-3, granulocyte-macrophage-colony stimulating factor (GM-CSF), and stem cell factor (SGM3 mice). hu-mSCF and SGM3 mice showed enhanced engraftment of human leukocytes compared to NSG mice, and this was reflected in the number of human neutrophils and monocytes present in these strains. Importantly, discrete classical, intermediate, and nonclassical monocyte populations were identifiable in the blood of NSG and hu-mSCF mice, while the nonclassical population was absent in the blood of SGM3 mice. Granulocyte-colony stimulating factor (GCSF) treatment increased the number of blood monocytes in NSG and hu-mSCF mice, and neutrophils in NSG and SGM3 mice; however, this effect appeared to be at least partially dependent on the stem cell donor used to engraft the mice. Furthermore, GCSF treatment resulted in a preferential expansion of nonclassical monocytes in both NSG and hu-mSCF mice. Human tubulointerstitial CD11c(+) cells were present in the kidneys of hu-mSCF mice, while monocytes and neutrophils were identified in the liver of all strains. Bone marrow-derived macrophages prepared from NSG mice were most effective at phagocytosing polystyrene beads. In conclusion, hu-mSCF mice provide the best environment for the generation of human myeloid cells, with GCSF treatment further enhancing peripheral blood human monocyte cell numbers in this strain.