Comparison of human cord blood engraftment between immunocompromised mouse strains
Comparison of human cord blood engraftment between immunocompromised mouse strains
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DOI：
10.1182/blood-2010-02-271841
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发表时间：
2010-07-15
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：
McDermott, Sean P.;Eppert, Kolja;Dick, John E.
非肥胖型糖尿病/重症联合免疫缺陷（NOD - scid）异种移植模型是检测人类造血干细胞活性的“金标准”。一些系统性的改进，例如用抗CD122抗体清除自然杀伤细胞活性、直接股骨内注射以及白细胞介素2受体γ（IL2Rγ）的缺失或截断，已经提高了人类细胞的植入；然而，这些小鼠模型是否等效，如果不等效，哪种模型在检测造血干细胞活性方面更优，这些问题仍然存在。为了解决这个问题，我们通过直接股骨内注射近极限剂量的谱系耗竭的人类脐带血细胞到NOD/Lt - scid、NOD/Shi - scid、NOD/Lt - scid/IL2Rγ（null）（NSG）以及NOD/Shi - scid/IL2Rγ（null）小鼠体内，比较了总体植入情况和多谱系分化情况。与其他品系相比，移植到NSG小鼠体内在骨髓中产生了适度更高的人类细胞植入水平。在极限剂量下，与NOD/Lt - scid小鼠相比，两种性别的NSG小鼠在检测重症联合免疫缺陷（SCID） - 再增殖细胞方面的敏感度高3.6倍。然而，在极限细胞剂量下，NSG雌性小鼠表现出更高的植入水平，导致SCID - 再增殖细胞检测总体提高9倍。与NOD/Lt - scid和NOD/Shi - scid小鼠相比，NSG和NOD/Shi - scid/IL2Rγ（null）都显著提高了外周组织的植入情况，而NSG小鼠在骨髓中的人类细胞植入比所有其他品系都要高，尤其是在极限剂量下。（《血液》2010年；116(2): 193 - 200）
The nonobese diabetic/severe combined immune deficiency (NOD-scid) xenotransplantation model is the "gold standard" for assaying human hematopoietic stem cell activity. Systematic advancements, such as depletion of natural killer cell activity with anti-CD122 antibody, direct intrafemoral injection, and deletion or truncation of IL2R gamma, have improved human cell engraftment; however, questions remain whether these mouse models are equivalent or, if not, which model is superior for assaying hematopoietic stem cell activity. To address this, we compared overall engraftment and multi-lineage differentiation of near-limiting doses of lineage-depleted human umbilical cord blood cells by direct intrafemoral injection into NOD/Lt-scid, NOD/Shi-scid, NOD/Lt-scid/IL2R gamma(null) (NSG), and NOD/Shi-scid/IL2R gamma(null) mice. Transplantation into NSG mice generated moderately higher human engraftment levels in bone marrow compared with other strains. At limiting doses, NSG mice of both sexes were 3.6-fold more sensitive in detecting SCID-repopulating cells compared with NOD/Lt-scid mice. However, NSG females exhibited higher engraftment at limiting cell doses, resulting in an overall increase in SCID-repopulating cell detection of 9-fold. Both NSG and NOD/Shi-scid/IL2R gamma(null) support significantly improved engraftment in peripheral tissues compared with NOD/Lt-scid and NOD/Shi-scid mice, whereas NSG mice provide greater human engraftment in bone marrow than all other strains, especially at limiting doses. (Blood. 2010; 116(2): 193-200)