New Experimental Model of Brain Tumors in Brains of Adult Immunocompetent Rats.

ABSTRACT

Aims: Xenograft models, namely heterotransplantation of human cancer cells or tumor biopsies into immunodeficient rodents are the major preclinical approach for the development of novel cancer therapeutics. However, in these models the animals must be used only after the severe systemic immune suppression in order to ensure graft survival. Thus, additional new human brain tumor models without immune suppression of the recipient rodent may be required. Place and Duration of Study Laboratory of Immunochemistry, V.P. Serbsky National Research Centre for Social and Forensic Psychiatry and Department of Nanobiotechnology, N.I. Pirogov Russian State Medical University and Department of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics between June 2009 and July 2010. Methodology: Brain tumor modeling was performed by intracerebral stereotactic implantation of cells to the healthy adult rats without any artificial immunodepression. Cells were implanted to the striatum region of ketamine-anesthetized rats at specific coordinates according to Swanson's rat brain atlas. Tumor growth was monitored weekly via registration of neurological signs and in vivo Bruker MRI system. Results: On the 21st day after implantation of C6 glioma, U251 or 293_CHI3L1 cells severe neurological deficit appeared in rats. Huge intracerebral tumors were found in each animal under investigation while no tumor growth was observed for at least 8 weeks in rats injected with empty vector-transfected 293 cells. Tumors contained the dense superficial cell layer and prominent lobules with central newly ingrowing blood vessels. Histological assay revealed displacement of median cerebral structures and hydrocephalus in contralateral hemisphere. All tumors were surrounded by numerous GFAP-positive reactive astrocytes. Conclusion: Positive results with transplantation of 293_CHI3L1 cells into adult rat brains without any immunosupression show the validity of this animal model. In all experiments such implantations provoked malignant tumor formation while there were no visible tumors in control rats. We believe this to be the first animal model of human brain tumor that displays the possibility to study various biologic features of and host therapeutic response to brain tumor in an immunocompetent host.