Establishment of a Novel Bladder Cancer Xenograft Model in Humanized Immunodeficient Mice

Establishment of a Novel Bladder Cancer Xenograft Model in Humanized Immunodeficient Mice
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DOI:
10.1159/000430401
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发表时间:
2015-01-01
影响因子:
--
通讯作者:
Han, Conghui
Han, Conghui
中科院分区:
医学1区
文献类型:
--
作者:
Gong, Zhen;Xu, Hanzi;Han, Conghui

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背景/目标:本研究的目的是通过将人膀胱癌异种移植物移植到人源化免疫缺陷小鼠(SCID)中来建立一种新的模型。研究方法:动物首先经历亚致死辐射,然后经历人淋巴细胞的同时移植(5x 107个细胞/小鼠i.p.)和人膀胱癌细胞(3 × 106个细胞/小鼠皮下)。结果:12只小鼠移植膀胱癌BIU-87细胞后均形成移植瘤,并对肿瘤标本进行组织学评价。所有6只模型小鼠的外周血、脾脏和异种移植物中均表达人CD3 mRNA和/或蛋白。移植接种后第6周,人CD3(+)细胞的平均比例为19%,外周血中人IgG水平为532.4 μ g/ml。通过对这些小鼠的增殖、分泌和细胞毒性反应进行单独体外测试,证实这些小鼠中重建的人免疫系统具有功能。结论:成功的移植人膀胱癌异种移植物和建立的人免疫系统在我们的体内模型在这里描述的可能提供了一个有用的工具,针对膀胱癌的新的治疗策略的发展。版权所有(C)2015 S. Karger AG,巴塞尔
Background/Aims: The aim of this study was to develop a novel model by transplanting human bladder cancer xenografts into humanized immunodeficient mice (SCID). Methods: The animals first underwent sublethal irradiation and then were subjected to simultaneous transplantation of human lymphocytes (5 x 107 cells/mouse i.p.) and human bladder cancer cells (3 x 106 cells/mouse s.c.). Results: The xenografts developed in all 12 mice that had received bladder cancer BIU-87 cells, and the tumor specimens were evaluated histologically. All 6 model mice expressed human CD3 mRNA and/or protein in the peripheral blood, spleens and xenografts. The mean proportion of human CD3(+) cells was 19% with a level of human IgG 532.4 mu g/ml in the peripheral blood at Week 6 after transplant inoculation. The re-constructed human immune system in these mice was confirmed to be functional by individual in vitro testing of their proliferative, secretory and cytotoxic responses. Conclusion: The successful engraftment of the human bladder cancer xenografts and the establishment of the human immune system in our in vivo model described here may provide a useful tool for the development of novel therapeutic strategies targeting at bladder cancer. Copyright (C) 2015 S. Karger AG, Basel