A Xenotransplant Model of Human Brain Tumors in Wild-Type Mice

Abstract

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.