Human pontine glioma cells can induce murine tumors.
Human pontine glioma cells can induce murine tumors.
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DOI：
10.1007/s00401-014-1272-4
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发表时间：
2014
影响因子：
12.7
通讯作者：
Wurdinger T
中科院分区：
文献类型：
--
作者：
Caretti V;Sewing AC;Lagerweij T;Schellen P;Bugiani M;Jansen MH;van Vuurden DG;Navis AC;Horsman I;Vandertop WP;Noske DP;Wesseling P;Kaspers GJ;Nazarian J;Vogel H;Hulleman E;Monje M;Wurdinger T
弥漫性内在脑桥胶质瘤（DIPG）的中位生存期仅为9个月，是儿童脑癌死亡的主要原因。直到最近，用于研究的肿瘤组织的切除限制了这种疾病的进展。DIPG研究的新实验模型正在出现。为了开发DIPG的临床前模型，采用了两种不同的方法：1）将尸检时获得的细胞直接原位异种移植到免疫缺陷小鼠的脑桥中，而没有干预细胞培养步骤，或2）首先在体外培养，并在成功扩增后，体内注射。这两种策略导致脑桥肿瘤的组织病理学类似于原始的人类DIPG肿瘤。然而，在直接移植方法之后，所有肿瘤被证明由鼠细胞而不是人细胞组成。这与包括初始体外培养并产生由人细胞组成的异种移植物的间接方法相反。值得注意的是，直接注射死后从未受癌症影响的人脑脑桥和额叶获得的细胞不会引起肿瘤。小鼠脑桥肿瘤表现出与人DIPG相似的免疫表型，但小胶质细胞/巨噬细胞标志物也呈阳性，如CD 45、CD 68和CD 11b。连续原位注射这些鼠细胞导致受体小鼠中的致死性肿瘤。在体内直接注射人DIPG细胞可引起恶性小鼠肿瘤。这代表了DIPG异种移植模型的重要警告。相反，初始体外培养步骤可以允许建立人原位异种移植物。在直接异种移植中观察到的这种现象的机制仍然是一个悬而未决的问题。
Diffuse intrinsic pontine glioma (DIPG), with a median survival of only nine months, is the leading cause of pediatric brain cancer mortality. Dearth of tumor tissue for research has limited progress in this disease until recently. New experimental models for DIPG research are now emerging. To develop preclinical models of DIPG, two different methods were adopted: cells obtained at autopsy 1) were directly xenografted orthotopically into the pons of immunodeficient mice without an intervening cell culture step or 2) were first cultured in vitro and, upon successful expansion, injected in vivo. Both strategies resulted in pontine tumors histopathologically similar to the original human DIPG tumors. However, following the direct transplantation method all tumors proved to be composed of murine and not of human cells. This is in contrast to the indirect method that included initial in vitro culture and resulted in xenografts comprised of human cells. Of note, direct injection of cells obtained post mortem from the pons and frontal lobe of human brains not affected by cancer did not give rise to neoplasms. The murine pontine tumors exhibited an immunophenotype similar to human DIPG, but were also positive for microglia/macrophage markers, such as CD45, CD68 and CD11b. Serial orthotopic injection of these murine cells results in lethal tumors in recipient mice. Direct injection of human DIPG cells in vivo can give rise to malignant murine tumors. This represents an important caveat for xenotransplantation models of DIPG. In contrast, an initial in vitro culture step can allow establishment of human orthotopic xenografts. The mechanism underlying this phenomenon observed with direct xenotransplantation remains an open question.
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影响因子：
3.7
作者：
Goldenberg DM;Gold DV;Loo M;Liu D;Chang CH;Jaffe ES
通讯作者：
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TSAO, MC