The development of adequate model systems to study human malignancies is crucial for basic and preclinical research. Here, we exploit the “immune-privileged” developmental time window to achieve orthotopic xenotransplantation of human brain tumor cells in wild-type (WT) mice. We find that, when transplanted in utero, human glioblastoma (GBM) cells readily integrate in the embryonic mouse brain mirroring key tumor-associated pathological features such as infiltration, vascularization, and complex tumor microenvironment including reactive astrocytes and host immune cell infiltration. Remarkably, activation of the host IBA1 tumor-associated microglia/macrophages depends on the type of glioma cell transplanted, suggesting our approach allows one to study human GBM interactions with the immune system of WT host mice. The embryonic engraftment model complements existing ones, providing a rapid and valuable alternative to study fundamental biology of human brain tumors in immune competent mice.

开发适当的模型系统以研究人类恶性肿瘤对基础和临床前研究至关重要。在这里，我们利用“免疫特权”的发育时间窗口来实现野生型（WT）小鼠中人脑肿瘤细胞的原位异种移植。我们发现，当移植到子宫内时，人类胶质母细胞瘤（GBM）细胞可以很容易地整合到胚胎小鼠的大脑中，从而反映出与肿瘤相关的关键病理特征，例如浸润，血管生成和复杂的肿瘤微环境，包括反应性星形胶质细胞和宿主免疫细胞浸润。值得注意的是，宿主IBA1肿瘤相关的小胶质细胞/巨噬细胞的激活取决于所移植的神经胶质瘤细胞的类型，这表明我们的方法允许研究人GBM与WT宿主小鼠免疫系统的相互作用。胚胎植入模型对现有模型进行了补充，为研究免疫能力强的小鼠中人脑肿瘤的基础生物学提供了一种快速而有价值的替代方法。