Diffuse Instrinsic Pontine
Glioma is the most aggressive form of High Grade
Gliomas in children. The lack of biological material and the absence of relevant models have hampered the development of new
therapeutics. Their extensive infiltration of the brainstem renders any surgical resection impossible and until recently biopsies were considered not informative enough and therefore not recommended. Thus, most models were derived from autopsy material. We aimed to develop relevant in vivo
DIPG models that mimic this specific disease and its molecular diversity from
tumor material obtained at diagnosis. Eight patient-derived orthotopic xenograft models were obtained after direct stereotactic injection of a mixed cell
suspension containing
tumor cells and stromal cells in the brainstem or thalamus of nude mice and serially passaged thereafter. In parallel, we developed 6 cell-derived xenograft models after orthotopic injection of tumor-initiating cells cultured from stereotactic biopsies. Cells were modified to express
luciferase to enable longitudinal
tumor growth monitoring, and fluorescent reporter
proteins to trace the
tumor cells in the brain. These models do not form a
tumor mass, they are invasive, show the H3K27 trimethylation loss in vivo and the
tumor type diversity observed in patients in terms of
histone H3 mutations and lineage markers. Histological and MRI features at 11.7 Tesla show similarities with treatment naïve human
DIPG, and in this respect, both direct and indirect orthotopic xenograft looked alike. These
DIPG models will therefore constitute valuable tools for evaluating new therapeutic approaches in this devastating disease.