From the Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Department of Pathology, The Ohio State University, Columbus, Ohio, USA.
J Neuropathol Exp Neurol. 2022 Apr 27;81(5):312-329. doi: 10.1093/jnen/nlac021.
Rodent brain tumor models have been useful for developing effective therapies for glioblastomas (GBMs). In this review, we first discuss the 3 most commonly used rat brain tumor models, the C6, 9L, and F98 gliomas, which are all induced by repeated injections of nitrosourea to adult rats. The C6 glioma arose in an outbred Wistar rat and its potential to evoke an alloimmune response is a serious limitation. The 9L gliosarcoma arose in a Fischer rat and is strongly immunogenic, which must be taken into consideration when using it for therapy studies. The F98 glioma may be the best of the 3 but it does not fully recapitulate human GBMs because it is weakly immunogenic. Next, we discuss a number of mouse models. The first are human patient-derived xenograft gliomas in immunodeficient mice. These have failed to reproduce the tumor-host interactions and microenvironment of human GBMs. Genetically engineered mouse models recapitulate the molecular alterations of GBMs in an immunocompetent environment and "humanized" mouse models repopulate with human immune cells. While the latter are rarely isogenic, expensive to produce, and challenging to use, they represent an important advance. The advantages and limitations of each of these brain tumor models are discussed. This information will assist investigators in selecting the most appropriate model for the specific focus of their research.
啮齿动物脑肿瘤模型在开发胶质母细胞瘤（GBM）的有效疗法方面非常有用。在这篇综述中，我们首先讨论了最常用的三种大鼠脑肿瘤模型，即 C6、9L 和 F98 胶质瘤，它们都是通过对成年大鼠反复注射亚硝脲诱导产生的。C6 胶质瘤起源于杂交 Wistar 大鼠，其引发同种异体免疫反应的潜力是一个严重的限制。9L 神经胶质瘤起源于 Fischer 大鼠，具有很强的免疫原性，在将其用于治疗研究时必须考虑到这一点。F98 胶质瘤可能是这三种模型中最好的，但它不能完全重现人类 GBM，因为它的免疫原性较弱。接下来，我们讨论了一些小鼠模型。首先是在免疫缺陷小鼠中移植的人类患者来源的异种移植物胶质瘤。这些模型未能重现人类 GBM 的肿瘤-宿主相互作用和微环境。遗传工程小鼠模型在免疫活性环境中重现了 GBM 的分子改变，而“人源化”小鼠模型则用人类免疫细胞重新填充。虽然后者很少是同基因的，生产成本高，使用起来具有挑战性，但它们代表了一个重要的进步。我们讨论了这些脑肿瘤模型的优缺点。这些信息将帮助研究人员为他们特定的研究重点选择最合适的模型。
