A novel immunodeficient rat model supports human lung cancer xenografts
A novel immunodeficient rat model supports human lung cancer xenografts
复制标题
一种新型免疫缺陷大鼠模型支持人肺癌异种移植
DOI：
10.1096/fj.201800102rr
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发表时间：
2019-01-01
期刊：
影响因子：
4.8
通讯作者：
Zhu, Xianmin
中科院分区：
文献类型：
--
作者：
He, Di;Zhang, Junhui;Zhu, Xianmin
患者来源的异种移植（PDX）动物模型允许人类肿瘤的外源性生长，为肿瘤学研究提供了不可替代的临床前工具。小鼠是人类PDX模型最常用的宿主，然而其较小的体型限制了异种移植物生长、样品收集和药物评价。因此，我们试图开发一种新的大鼠模型，可以克服许多这些限制。我们通过成簇规则间隔短回文重复序列（CRISPR）-CRISPR相关蛋白9技术敲除Sprague道利（SD）大鼠中的Rag 1、Rag 2和Il 2 rg。Rag 1（-/-）Rag 2（-/-）Il 2 rg（-/Y）（指定为SD-RG）大鼠的淋巴器官发育显著受损。因此，SD-RG大鼠严重免疫缺陷，免疫系统中缺乏成熟的T、B和NK细胞。皮下注射不同来源的肿瘤细胞系，如NCI-H460、U-87 MG和MDA-MB-231后，SD-RG大鼠中的肿瘤生长明显快于非肥胖糖尿病-Cg-Prkdc（scid）Il 2 rg（tm 1 Wjl）/SzJ小鼠，并且生长得更大。最重要的是，我们成功地建立了肺鳞状细胞癌的PDX模型，其中移植物再现了原发肿瘤的组织病理学特征。总之，与小鼠相比，严重免疫缺陷的SD-RG大鼠支持PDX的快速生长，因此具有作为肿瘤学研究的新模型的巨大潜力。Zhang，J.，吴伟，Yi，N.，他，W.，卢，P.，Li，B.，杨，N.，Wang，D.，中国科学院，薛志，张，P.，Fan，G.，Zhu，X.一种新的免疫缺陷大鼠模型支持人肺癌异种移植。
Patient-derived xenograft (PDX) animal models allow the exogenous growth of human tumors, offering an irreplaceable preclinical tool for oncology research. Mice are the most commonly used host for human PDX models, however their small body size limits the xenograft growth, sample collection, and drug evaluation. Therefore, we sought to develop a novel rat model that could overcome many of these limitations. We knocked out Rag1, Rag2, and Il2rg in Sprague Dawley (SD) rats by clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 technology. The development of lymphoid organs is significantly impaired in Rag1(-/-)Rag2(-/-)Il2rg(-/Y) (designated as SD-RG) rats. Consequently, SD-RG rats are severely immunodeficient with an absence of mature T, B, and NK cells in the immune system. After subcutaneous injection of tumor cell lines of different origin, such as NCI-H460, U-87MG, and MDA-MB-231, the tumors grow significantly faster and larger in SD-RG rats than in nonobese diabetic-Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. Most important of all, we successfully established a PDX model of lung squamous cell carcinoma in which the grafts recapitulate the histopathologic features of the primary tumor for several passages. In conclusion, the severely immunodeficient SD-RG rats support fast growth of PDX compared with mice, thus holding great potential to serve as a new model for oncology research.He, D., Zhang, J., Wu, W., Yi, N., He, W., Lu, P., Li, B., Yang, N., Wang, D., Xue, Z., Zhang, P., Fan, G., Zhu, X. A novel immunodeficient rat model supports human lung cancer xenografts.