Morgridge Institute for Research, Madison, WI 53715, USA.
Department of Surgery, University of Wisconsin, Madison, WI 53715, USA.
Stem Cell Reports. 2015 Feb 10;4(2):171-80. doi: 10.1016/j.stemcr.2014.12.005. Epub 2015 Jan 15.
In this study, we demonstrate a newly derived mouse model that supports engraftment of human hematopoietic stem cells (HSCs) in the absence of irradiation. We cross the NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) strain with the C57BL/6J-Kit(W-41J)/J (C57BL/6.Kit(W41)) strain and engraft, without irradiation, the resulting NBSGW strain with human cord blood CD34+ cells. At 12-weeks postengraftment in NBSGW mice, we observe human cell chimerism in marrow (97% ± 0.4%), peripheral blood (61% ± 2%), and spleen (94% ± 2%) at levels observed with irradiation in NSG mice. We also detected a significant number of glycophorin-A-positive expressing cells in the developing NBSGW marrow. Further, the observed levels of human hematopoietic chimerism mimic those reported for both irradiated NSG and NSG-transgenic strains. This mouse model permits HSC engraftment while avoiding the complicating hematopoietic, gastrointestinal, and neurological side effects associated with irradiation and allows investigators without access to radiation to pursue engraftment studies with human HSCs.
在这项研究中，我们展示了一种新衍生的小鼠模型，该模型支持在不进行照射的情况下植入人造血干细胞（HSCs）。我们将 NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ（NSG）品系与 C57BL/6J-Kit(W-41J)/J（C57BL/6.Kit(W41)）品系杂交，并在不进行照射的情况下将所得的 NBSGW 品系与人类脐带血 CD34+细胞一起植入。在 NBSGW 小鼠植入后 12 周，我们观察到骨髓（97%±0.4%）、外周血（61%±2%）和脾脏（94%±2%）中的人细胞嵌合率与 NSG 小鼠照射后的水平相当。我们还在发育中的 NBSGW 骨髓中检测到大量表达糖蛋白 A 的细胞。此外，观察到的人造血嵌合水平与已报道的辐照 NSG 和 NSG 转基因品系相似。这种小鼠模型允许 HSC 植入，同时避免了与照射相关的复杂的造血、胃肠道和神经副作用，并允许没有辐射设备的研究人员进行人 HSC 的植入研究。
