Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation.
The initial aim of this study was to generate a transplantable glial tumour model of low-intermediate grade by disaggregation of a spontaneous tumour mass from genetically engineered models (GEM). This should result in an increased tumour incidence in comparison to GEM animals. An anaplastic oligoastrocytoma (OA) tumour of World Health Organization (WHO) grade III was obtained from a female GEM mouse with the S100β-v-erbB/inK4a-Arf (+/-) genotype maintained in the C57BL/6 background. The tumour tissue was disaggregated; tumour cells from it were grown in aggregates and stereotactically injected into C57BL/6 mice. Tumour development was followed using Magnetic Resonance Imaging (MRI), while changes in the metabolomics pattern of the masses were evaluated by Magnetic Resonance Spectroscopy/Spectroscopic Imaging (MRS/MRSI). Final tumour grade was evaluated by histopathological analysis. The total number of tumours generated from GEM cells from disaggregated tumour (CDT) was 67 with up to 100 % penetrance, as compared to 16 % in the local GEM model, with an average survival time of 66 ± 55 days, up to 4.3-fold significantly higher than the standard GL261 glioblastoma (GBM) tumour model. Tumours produced by transplantation of cells freshly obtained from disaggregated GEM tumour were diagnosed as WHO grade III anaplastic oligodendroglioma (ODG) and OA, while tumours produced from a previously frozen sample were diagnosed as WHO grade IV GBM. We successfully grew CDT and generated tumours from a grade III GEM glial tumour. Freezing and cell culture protocols produced progression to grade IV GBM, which makes the developed transplantable model qualify as potential secondary GBM model in mice.
Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Edifici Cs, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Cerdanyola del Vallès, Spain.
Magdalena
M
Ciezka
Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Edifici Cs, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Cerdanyola del Vallès, Spain.
Milena
M
Acosta
Laboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.|Research and Development Unit, Cell Therapy Program, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Cristina
C
Herranz
Laboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.|Research and Development Unit, Cell Therapy Program, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Josep M
JM
Canals
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Cerdanyola del Vallès, Spain.|Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Edifici V, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain.
Martí
M
Pumarola
Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Edifici Cs, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain. AnaPaula.Candiota@uab.cat.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Cerdanyola del Vallès, Spain. AnaPaula.Candiota@uab.cat.|Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain. AnaPaula.Candiota@uab.cat.
Ana Paula
AP
Candiota
Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Edifici Cs, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Cerdanyola del Vallès, Spain.|Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain.
Carles
C
Arús
D000818:Animals; D030801:Animals, Genetically Modified; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008810:Mice, Inbred C57BL / Q000235:genetics*; D060787:Neoplasm Grading; D009837:Oligodendroglioma / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D016019:Survival Analysis
Disaggregated tumour; Molecular imaging; Preclinical brain tumour; Secondary glioblastoma