Rabbit Model of Human Gliomas: Implications for Intra-Arterial Drug Delivery

• Published in: PloS one Vol. 12; no. 1; p. e0169656
• Main Authors: Qin, Huamin, Janowski, Miroslaw, Pearl, Monica S, Malysz-Cymborska, Izabela, Li, Shen, Eberhart, Charles G, Walczak, Piotr
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19-01-2017; Public Library of Science (PLoS)
• Subjects: Animals; Antigens; Biology and Life Sciences; Blood-brain barrier; Blood-Brain Barrier - drug effects; Body weight; Brain cancer; Brain Neoplasms - blood supply; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - drug therapy; Brain research; Brain tumors; Care and treatment; Cell Line, Tumor; Chemical compounds; Chemotherapy; Dexamethasone; Diagnosis; Disease Models, Animal; Drug delivery; Drug Delivery Systems; Engineering; Glioblastoma; Glioma; Glioma - blood supply; Glioma - diagnostic imaging; Glioma - drug therapy; Gliomas; Health aspects; Heterografts; Histopathology; Humans; Immunohistochemistry; Immunosuppression; Immunosuppressive agents; Infusions, Intra-Arterial; Magnetic Resonance Imaging; Mannitol; Mannitol - administration & dosage; Medicine; Medicine and Health Sciences; Metastasis; Modelling; Mycophenolate mofetil; Mycophenolic acid; Neuroimaging; Neurosurgery; Osmolar Concentration; Osmotic pressure; Pharmacology; Prognosis; Rabbits; Radiation therapy; Radiology; Research and Analysis Methods; Risk factors; Science; Surgery; Tacrolimus; Tumor cells; Tumors; Xenografts; Xenotransplantation; New Zealand
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0169656

The prognosis for malignant brain tumors remains poor despite a combination of surgery, radiotherapy, and chemotherapy. This is partly due to the blood-brain barrier, a major obstacle that prevents therapeutic agents from effectively reaching the tumor. We have recently developed a method for precise and predictable opening of the blood-brain barrier via the intra-arterial administration of mannitol, a hyperosmolar agent, in a rabbit model, whose vascular anatomy facilitates the use of standard interventional neuroradiology techniques and devices. To date, however, no protocols are available that enable human glioma modeling in rabbits. In this article, we report on the xenotransplantation of a human glioblastoma (GBM-1) in adult New Zealand rabbits. We induced multi-drug immunosuppression (Mycophenolate Mofetil, Dexamethasone, Tacrolimus) and stereotactically implanted GBM-1 tumor cells into rabbit brains. The rabbits were followed for 42 days, monitored by MRI and body weight measurements, and underwent postmortem histopathological analysis. On MRI, brain tumors were identified on T2-weighted scans. On histopathology, tumors were detected with hematoxylin/eosin and their human origin was confirmed with immunohistochemistry against human-specific antigens. Our method for human glioma modeling in rabbits provides the foundation to test novel treatment strategies, including intra-arterial therapeutic agent delivery.