Case Comprehensive Cancer Center, National Center for Regenerative Medicine, Seidman Cancer Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA.
Blood. 2012 Feb 16;119(7):1768-71. doi: 10.1182/blood-2011-05-350611. Epub 2011 Dec 6.
Although scid mice have been widely used for human HSC engraftment studies, the function of HSCs of scid mice has not been characterized. We hypothesized that the DNA repair defect of scid mice results in a stem cell defect that facilitates HSC engraftment. scid BM cells showed severely impaired repopulation potentials in the competitive repopulation assay. To assess the BM hematopoietic niche occupancy ability of scid HSC, WT BM cells were transplanted into scid mice without any conditioning and observed to achieve long-term engraftment. Furthermore, the defects of scid HSCs are independent of their inability to perform lymphopoiesis because a similar defect in hematopoietic niche occupancy was not observed with Rag1(-/-) recipients. These results demonstrate that scid HSCs are impaired in maintenance within the niche, which may explain the nature of the conducive marrow niche environment of scid mice for xenotransplantation.
虽然 scid 小鼠已被广泛用于人类 HSC 植入研究,但 scid 小鼠的 HSC 功能尚未得到表征。我们假设 scid 小鼠的 DNA 修复缺陷导致干细胞缺陷,从而促进 HSC 植入。在竞争性重建造血实验中,scidBM 细胞显示出严重受损的再群体潜力。为了评估 scid HSC 的 BM 造血龛位占据能力,将 WT BM 细胞移植到未经任何预处理的 scid 小鼠中,观察到其能够长期植入。此外,scid HSCs 的缺陷与其无法进行淋巴生成无关,因为在 Rag1(-/-) 受体中没有观察到造血龛位占据的类似缺陷。这些结果表明,scid HSCs 在龛位内的维持能力受损,这可能解释了 scid 小鼠有利于异种移植的骨髓龛环境的性质。