Engraftment of human hematopoietic stem cells is more efficient in female NOD/SCID/IL-2Rgc-null recipients
Engraftment of human hematopoietic stem cells is more efficient in female NOD/SCID/IL-2Rgc-null recipients
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DOI：
10.1182/blood-2009-10-249326
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发表时间：
2010-05-06
期刊：
影响因子：
20.3
通讯作者：
Dick, John E.
中科院分区：
文献类型：
--
作者：
Notta, Faiyaz;Doulatov, Sergei;Dick, John E.
免疫缺陷小鼠的再植入仍然是检测人类造血干细胞（HSCs）的主要方法。在此我们报道，与雄性受体相比，雌性NOD/SCID/IL - 2Rg(c) - 无小鼠在检测人类HSCs（Lin(-)CD34(+)CD38(-)CD90(+)CD45RA(-)）方面具有极大优势。当移植多个HSCs时，雌性受体显示出人类嵌合水平更高的趋势（1.4倍）（雌性与雄性相比：注射的股骨，44.4 ± 9.3对32.2 ± 6.2；雌性n = 12，雄性n = 24；P = 0.1）。显著的是，在有限细胞剂量下这种效应被极大地放大，其中雌性受体从单个HSCs获得的嵌合度大约高11倍（雌性与雄性相比：注射的股骨，8.1 ± 2.7对0.7 ± 0.7；雌性n = 28，雄性n = 20；P < 0.001）。来自原代受体的二次移植表明雌性更有效地支持人类HSCs的自我更新。因此，性别相关因素在异种移植模型中人类HSCs的存活、增殖和自我更新中起关键作用，并且在未来需要人类HSC检测的实验设计中必须仔细考虑受体性别。（《血液》2010年；115(18):3704 - 3707）
Repopulation of immunodeficient mice remains the primary method to assay human hematopoietic stem cells (HSCs). Here we report that female NOD/SCID/IL-2Rg(c)-null mice are far superior in detecting human HSCs (Lin(-)CD34(+)CD38(-)CD90(+)CD45RA(-)) compared with male recipients. When multiple HSCs were transplanted, female recipients displayed a trend (1.4-fold) toward higher levels of human chimerism (female vs male: injected femur, 44.4 +/- 9.3 vs 32.2 +/- 6.2; n = 12 females, n = 24 males; P = .1). Strikingly, this effect was dramatically amplified at limiting cell doses where female recipients had an approximately 11-fold higher chimerism from single HSCs (female vs male: injected femur, 8.1 +/- 2.7 vs 0.7 +/- 0.7; n = 28 females, n = 20 males; P < .001). Secondary transplantations from primary recipients indicate that females more efficiently support the self-renewal of human HSCs. Therefore, sex-associated factors play a pivotal role in the survival, proliferation, and self-renewal of human HSCs in the xenograft model, and recipient sex must be carefully monitored in the future design of experiments requiring human HSC assays. (Blood. 2010; 115(18):3704-3707)