Development of induced glioblastoma by implantation of a human xenograft in Yucatan minipig as a large animal model

Publication date: Available online 9 March 2017
Source:Journal of Neuroscience Methods
Author(s): Mehrdad Khoshnevis, Claude Carozzo, Catherine Bonnefont-Rebeix, Sara Belluco, Olivia Leveneur, Thomas Chuzel, Elodie Pillet-Michelland, Matthieu Dreyfus, Thierry Roger, François Berger, Frédérique Ponce
BackgroundGlioblastoma is the most common and deadliest primary brain tumor for humans. Despite many efforts toward the improvement of therapeutic methods, prognosis is poor and the disease remains incurable with a median survival of 12-14.5 months after an optimal treatment. To develop novel treatment modalities for this fatal disease, new devices must be tested on an ideal animal model before performing clinical trials in humans.New methodA new model of induced glioblastoma in Yucatan minipigs was developed. Nine immunosuppressed minipigs were implanted with the U87 human glioblastoma cell line in both the left and right hemispheres. Computed tomography (CT) acquisitions were performed once a week to monitor tumor growth.ResultsAmong the 9 implanted animals, 8 minipigs showed significant macroscopic tumors on CT acquisitions. Histological examination of the brain after euthanasia confirmed the CT imaging findings with the presence of an undifferentiated glioma.Comparison with existing methodYucatan minipig, given its brain size and anatomy (gyrencephalic structure) which are comparable to humans, provides a reliable brain tumor model for preclinical studies of different therapeuticmethodsin realistic conditions. Moreover, the short development time, the lower cyclosporine and caring cost and the compatibility with the size of commercialized stereotactic frames make it an affordable and practical animal model, especially in comparison with large breed pigs.ConclusionThis reproducible glioma model could simulate human anatomical conditions in preclinical studies and facilitate the improvement of novel therapeutic devices, designed at the human scale from the outset.



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