Visualization of 5T33 myeloma cells in the C57BL/KaLwRij mouse: Establishment of a new syngeneic murine model of multiple myeloma
Visualization of 5T33 myeloma cells in the C57BL/KaLwRij mouse: Establishment of a new syngeneic murine model of multiple myeloma
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DOI：
10.1016/j.exphem.2004.07.019
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发表时间：
2004-11-01
影响因子：
2.6
通讯作者：
Abedi-Valugerdi, M
中科院分区：
文献类型：
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作者：
Alici, E;Konstantinidis, KV;Abedi-Valugerdi, M
objective.缺乏良好的模型，在体内检测多发性骨髓瘤（MM）细胞阻碍了我们对疾病的理解。我们的目的是建立一个小鼠模型MM，允许敏感和劳动免费跟踪和定量的MM细胞在免疫活性主机。逆转录病毒转导5T33 MM细胞，表达增强型绿色荧光蛋白（eGFP）和/或单纯疱疹病毒胸苷激酶（HSV-tk）作为对照。评估流式细胞术eGFP检测的准确性和灵敏度。转导细胞的功能特性，包括生长速率和生产的IgG 2b副蛋白和白细胞介素-6，进行了比较，那些非转导细胞在体外。为了诱导MM，向C57 BL/KaLwRij小鼠静脉内注射转导和未转导的细胞。评估eGFP细胞的存活动力学和在组织中的分布。流式细胞术eGFP检测在1：1000转导/未转导细胞比率下是准确的。转导和非转导的5T33 MM细胞表现出相似的生长速率，产生相当的IgG2b和白细胞介素-6水平。向C57 BL/KaLwRij小鼠静脉内注射未转导的和eGFP转导的MM细胞导致截瘫。在截瘫时，在骨髓、脾和肝中大量检测到eGFP转导的MM细胞，在淋巴结中较少，但在胸腺中未检测到。与非截瘫动物相比，截瘫小鼠骨髓中含有更高的eGFP转导的MM细胞。在建立的eGFP-5T33 MM模型中，MM细胞在免疫活性宿主中容易追踪。该模型简化了归巢模式研究的分析，各种治疗方法的治疗效果的评价，并有助于更好地理解MM。（C）2004年国际实验血液学学会。爱思唯尔公司出版
Objective. Lack of good models for in vivo detection of multiple myeloma (MM) cells hampers our understanding of the disease. Our objective was to establish a murine model for MM, allowing sensitive and labor-free tracing and quantification of MM cells in an immunocompetent host.Methods. 5T33MM cells were retrovirally transduced, expressing enhanced green fluorescent protein (eGFP) and/or herpes simplex virus thymidine kinase (HSV-tk) as a control. Flow cytometric eGFP detection accuracy and sensitivity were assessed. Functional characteristics of transduced cells, including growth rate and production of IgG2b paraprotein and interleukin-6, were compared to those of nontransduced cells in vitro. For induction of MM, C57BL/KaLwRij mice were injected intravenously with transduced and nontransduced cells. Survival kinetics and distribution of eGFP cells in tissues were evaluated.Results. Flow cytometric eGFP detection was accurate at 1:1000 transduced/nontransduced cell ratio. Transduced and nontransduced 5T33MM cells exhibited similar growth rates, producing comparable IgG2b and interleukin-6 levels. Intravenous injection of both nontransduced and eGFP-transduced MM cells to C57BL/KaLwRij mice resulted in paraplegia. At the time of paraplegia, eGFP-transduced MM cells were detected substantially in the bone marrow, spleen, and liver, less in lymph nodes, but not in the thymus. The bone marrow of paraplegic mice contained higher eGFP-transduced MM cells compared to that of nonparaplegic animals.Conclusions. In the established eGFP-5T33 MM model, MM cells are easily traced in an immunocompetent host. This model simplifies the analysis of homing pattern studies, the evaluation of therapeutic effects of various treatment approaches and contributes towards better understanding of MM. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.