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对患者来源的慢性粒单核细胞白血病细胞在NSGS小鼠中植入的影响。 (注:原文中“Effects of on”中间缺少具体内容)

Effects of on Engraftment of Patient-derived Chronic-Myelomonocytic Leukemia Cells in NSGS Mice.

作者信息

Vedder Alexis R, Miedel Emily L, Ragland Natalie H, Balasis Maria E, Letson Christopher T, Engelman Robert W, Padron Eric

出版信息

Comp Med. 2019 Aug 1;69(4):276-282. doi: 10.30802/AALAS-CM-18-000138. Epub 2019 Jul 26.

Abstract

Modeling chronic myelomonocytic leukemia (CMML) in immunodeficient NSGS mice relies on unique human CMML specimens and consistent murine engraftment. Only anecdotal comments have thus far supported the notion that research data may be altered by , an opportunistic cutaneous pathogen of immunodeficient mice. disseminated by asymptomatic and clinically affected mice with hyperkeratotic dermatitis, resulting in resilient facility contamination and infectious recurrence. Herein we report that, compared with PCR-negative counterparts, PCR-positive NSGS mice developed periocular and facial hyperkeratosis and alopecia and had reduced metrics indicative of ineffective human CMML engraftment, including less thrombocytopenia, less splenomegaly, fewer CMML infiltrates in histopathologic sections of murine organs, and fewer human CD45 cells in samples from murine spleen, bone marrow, and peripheral blood that were analyzed by flow cytometry. All CMML model metrics of engraftment were significantly reduced in the PCR-positive cohort compared with the negative cohort. In addition, a survey of comprehensive cancer center practices revealed that most murine facilities do not routinely test for or broadly decontaminate the facility or its equipment after a outbreak, thus increasing the likelihood of recurrence of invalidated studies. Our findings document that CMML engraftment of NSGS mice is diminished-and the integrity of murine research data jeopardized-by infection of immunodeficient mice. In addition, our results indicate that should be excluded from and not tolerated in murine facilities housing immunodeficient strains.

摘要

在免疫缺陷的NSGS小鼠中建立慢性粒单核细胞白血病(CMML)模型依赖于独特的人类CMML标本和一致的小鼠植入。迄今为止,只有一些传闻支持这样一种观点,即研究数据可能会被一种免疫缺陷小鼠的机会性皮肤病原体改变。这种病原体由无症状和临床受影响的患有角化过度性皮炎的小鼠传播,导致设施污染顽固且感染复发。在此我们报告,与PCR阴性的同窝小鼠相比,PCR阳性的NSGS小鼠出现眼周和面部角化过度及脱毛,且表明人类CMML植入无效的指标降低,包括血小板减少症减轻、脾肿大减轻、小鼠器官组织病理学切片中的CMML浸润减少,以及通过流式细胞术分析的小鼠脾脏、骨髓和外周血样本中的人类CD45细胞减少。与PCR阴性队列相比,PCR阳性队列中所有CMML模型的植入指标均显著降低。此外,一项对综合癌症中心实践的调查显示,大多数小鼠设施在爆发后不常规检测,也不广泛对设施或其设备进行去污,从而增加了无效研究复发的可能性。我们的研究结果表明,免疫缺陷小鼠的感染会降低NSGS小鼠的CMML植入,并危及小鼠研究数据的完整性。此外,我们的结果表明,在饲养免疫缺陷品系小鼠的设施中应排除并不能容忍。

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