Models for neuro-oncological preclinical studies: solid orthotopic and heterotopic grafts of human gliomas into nude mice.

To study the optimum therapeutic modalities for treating human malignant brain tumors in vivo without ethical limitations, a model of heterotopic and another of orthotopic xenografting into nude mice were developed. For the first implantation, 11 human high-grade gliomas and 4 low-grade tumors were microsurgically grafted on epigastric vessels. The 11 high-grade gliomas, but no low-grade tumors, were established into nude mice. Afterwards, all these mouse-adapted gliomas which grafted into other nude mice developed. Introduction of a microcatheter into the femoral artery or vein permitted infusion for magnetic resonance imaging (MRI) and treatment. A bladder catheter setting and electrode implantation allowed urine sampling and ECG or EEG recording. Thus, the most important parameters of chemo- and radiotherapy to destroy a maximum number of malignant cells or to inhibit their divisions and the hosts reactions to treatment can be studied. The human gliomas transplanted onto the mouse brain infiltrated the host brain at great distances from the tumor, as in human patients. So, this second implantation constitutes a representative model of the evolution of human gliomas, and allows the study of malignant cell migration in the brain before, during and after treatment determined with the heterotopic model and to appreciate the tolerance of the colonized brain to these treatments. Echography and MRI allowed us to follow the macroscopic evolution with or without treatment of the malignant brain tumors transplanted onto mouse brains. It should now be possible to undertake the same clinical studies on patients after appropriate consideration of ethical and scientific constraints.