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  • 标题:A Xenotransplant Model of Human Brain Tumors in Wild-Type Mice
  • 本地全文:下载
  • 作者:Nadin Hoffmann ; Virginia Fernández ; Rui Cruz Pereira
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2020
  • 卷号:23
  • 期号:1
  • 页码:1-24
  • DOI:10.1016/j.isci.2019.100813
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummaryThe 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 transplantedin 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.Graphical AbstractDisplay OmittedHighlights•Human glioblastoma cells quickly form tumors in brain of WT mouse embryos•Glioblastoma xenografts mirror several key characteristics of the original tumor•Host IBA1+ microglia/macrophages associate with glioblastoma xenografts•Activation of IBA1+ tumor-associated cells depends on the type of xenograftBiological Sciences; Cancer; Biological Sciences Research Methodologies; Model Organism
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