Mian Syed A, Ariza-McNaughton Linda, Anjos-Afonso Fernando, Guring Remisha, Jackson Sophie, Kizilors Aytug, Gribben John, Bonnet Dominique
Haematopoietic Stem Cell Lab The Francis Crick Institute London UK.
Laboratory for Molecular Haemato-Oncology King's College Hospital London London UK.
Hemasphere. 2024 May 21;8(5):e80. doi: 10.1002/hem3.80. eCollection 2024 May.
Immunodeficient mouse models are widely used for the assessment of human normal and leukemic stem cells. Despite the advancements over the years, reproducibility, as well as the differences in the engraftment of human cells in recipient mice remains to be fully resolved. Here, we used various immunodeficient mouse models to characterize the effect of donor-recipient sex on the engraftment of the human leukemic and healthy cells. Donor human cells and recipient immunodeficient mice demonstrate sex-specific engraftment levels with significant differences observed in the lineage output of normal CD34 hematopoietic stem and progenitor cells upon xenotransplantation. Intriguingly, human female donor cells display heightened sensitivity to the recipient mice's gender, influencing their proliferation and resulting in significantly increased engraftment in female recipient mice. Our study underscores the intricate interplay taking place between donor and recipient characteristics, shedding light on important considerations for future studies, particularly in the context of pre-clinical research.
免疫缺陷小鼠模型被广泛用于评估人类正常干细胞和白血病干细胞。尽管多年来取得了进展,但人类细胞在受体小鼠中的植入的可重复性以及差异仍有待完全解决。在这里,我们使用各种免疫缺陷小鼠模型来表征供体-受体性别对人类白血病细胞和健康细胞植入的影响。供体人类细胞和受体免疫缺陷小鼠表现出性别特异性的植入水平,在异种移植后正常CD34造血干细胞和祖细胞的谱系输出中观察到显著差异。有趣的是,人类女性供体细胞对受体小鼠的性别表现出更高的敏感性,影响它们的增殖并导致在雌性受体小鼠中的植入显著增加。我们的研究强调了供体和受体特征之间发生的复杂相互作用,为未来的研究,特别是临床前研究的重要考虑因素提供了启示。