Imaging and histological characterization of a human brain xenograft in pig: The first induced glioma model in a large animal

• Published in: Journal of neuroscience methods 2014-01, Vol.221, p.159-165
• Main Authors: Selek, Laurent, Seigneuret, Eric, Nugue, Guillaume, Wion, Didier, Nissou, Marie France, Salon, Caroline, Seurin, Marie José, Carozzo, Claude, Ponce, Frédérique, Roger, Thierry, Berger, François
• Format: Article
• Language: English
• Subjects: Animals; Brain Neoplasms - pathology; Cancer stem cells; Cell Line, Tumor - transplantation; Ciclosporine; Convection-enhanced delivery; Disease Models, Animal; Glioblastoma model; Glioma - pathology; Heterografts; Humans; Magnetic Resonance Imaging; Pig; Primates; Sus scrofa
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2013.10.002

•We have developed the first induced large animal glioma model.•Ciclosporine was used for the immunomodulation.•The time to develop a tumor is short and reproducible with U87 MG cells, allowing preclinical studies.•Pig and human brains are macroscopically similar, providing realistic condition for convection enhanced-delivery protocol. The prognosis of glioblastoma remains poor despite significant improvement in cytoreductive surgery, external irradiation and new approach of systemic treatment as antiangiogenic therapy. One of the issues is the low concentration in the infiltrated parenchyma of therapeutic agent administered intravenously mainly due to the blood–brain barrier. An intracerebral injection is advocated to overpass this barrier, this kind of administration need a low flow and continuous injection. The development of sophisticated implanted devices for convection-enhanced delivery is a mandatory step to have a controlled released of a therapeutic agent in glioblastoma treatment. Before testing such a device in a clinical trial a serious preclinical studies are required, in order to test it in realistic conditions we have develop the first induced high grade glioma model in a non-rodent animal: the pig. 21 pigs have been implanted in the parietal lobe with human glioblastoma cell lineage under a chemical immunosuppression by ciclosporine. A MRI follow up was then realized. 15 pigs have been implanted with U87MG, 14 have presented a macroscopic significant tumor, with radiological and anatomapathological characteristics of high grade glioma. 6 pigs were implanted with G6, stem-like cells tumors of glioblastoma, 1 pig develops a macroscopic tumor. This is the first reproducible glioma model in a large animal described, it open the way to preclinical studies to test implanted devices in anatomic realistic conditions, without the ethical issues of a primate use.