PM-01TDTM, THE ONLY MODEL TO BIOLOGICALLY REPRODUCE AND STUDY GLIOBLASTOMA DEVELOPMENT IN THE WHOLE BRAIN

The ideal animal model must enable us to biologically replicate and monitor all the dynamics of glioblastoma progression from the beginning to the end of its natural history both in the bulk and in the "apparently healthy" microinfiltrated brain parenchyma. The proposed model, called "The development tumor model" (TDTM), is a xenogeneic orthotopic transplantation model using GBM-derived cell lines from the pre-hypoxic phase of the founding clone (inferred after reconstruction of the phylogenetic tree) cultivated in a neurobasal serum-free medium as transplanted material. The model posits the transplantation of the same number of cells into several genetically identical immunocompromised rodents (an inbred strain of mice or rats) at the same time (time zero). Thus, the model creates a pool of twin immunodeficient transplant animals examined under the same conditions. By sacrificing one animal a week (or choosing any time interval as needed) during the progression of the tumor, we can follow and monitor the entire development of the glioblastoma both in the primary tumor and in the microinfiltrated brain parenchyma. The model can really mirror in one single generation of rodents the natural history of a patient affected by glioblastoma. Indeed, by using TDTM we can obtain multiple biopsies (in the bulk, ipsilateral hemisphere, corpus callosum, contralateral hemisphere) and stainings on sections at all the stages of glioblastoma development both in the bulk and in the microinfiltrated brain parenchyma. TDTM having the possibility to replicate all the steps of GBM progression and brain parenchyma infiltration, is perfectly suitable for studying the entire progression of the bulk and the fascinating concepts of settlement and dormancy (until activation) of CSCs in the parenchymal niche. By adopting TDTM, we can finally shed light on which specific cells and particular markers to focus on in order to find new effective therapeutic strategies.