Division of Stem Cell and Developmental Biology, Campbell Family Institute for Cancer Research/Ontario Cancer Institute, Toronto, ON, Canada.
Blood. 2010 May 6;115(18):3704-7. doi: 10.1182/blood-2009-10-249326. Epub 2010 Mar 5.
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.
免疫缺陷小鼠的重建仍然是检测人造血干细胞（HSCs）的主要方法。在这里，我们报告说，与雄性受体相比，雌性 NOD/SCID/IL-2Rg(c)-null 小鼠在检测人 HSCs（Lin(-)CD34(+)CD38(-)CD90(+)CD45RA(-)）方面要优越得多。当移植多个 HSCs 时，雌性受体会出现更高水平的人嵌合体（女性与男性：注射股骨，44.4 +/- 9.3 比 32.2 +/- 6.2；n = 12 名女性，n = 24 名男性；P =.1）的趋势。引人注目的是，这种效应在细胞剂量限制时被显著放大，在这种情况下，雌性受者从单个 HSCs 中获得的嵌合体大约高出 11 倍（女性与男性：注射股骨，8.1 +/- 2.7 比 0.7 +/- 0.7；n = 28 名女性，n = 20 名男性；P <.001）。来自原发性受者的二次移植表明，雌性受者更有效地支持人类 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着关键作用，在未来需要人类 HSC 检测的实验设计中，必须仔细监测受体的性别。
