Orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumors
Abstract Meningiomas are the most common primary central nervous system tumor. Clinical trials have failed to support effective medical treatments, despite initially promising animal studies. A key issue could be that available experimental models fail to mimic the clinical situation. Hence, there i...
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Nature Portfolio
2024-12-01
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| author | Mikkel Schou Andersen Bo Halle Martin Wirenfeldt Jeanette Krogh Petersen Morten Winkler Møller Philipp Jurmeister Birgitte Brinkmann Olsen Bjarne Winther Kristensen Henning Boldt Christian Bonde Pedersen Tiit Mathiesen Frantz Rom Poulsen |
| author_facet | Mikkel Schou Andersen Bo Halle Martin Wirenfeldt Jeanette Krogh Petersen Morten Winkler Møller Philipp Jurmeister Birgitte Brinkmann Olsen Bjarne Winther Kristensen Henning Boldt Christian Bonde Pedersen Tiit Mathiesen Frantz Rom Poulsen |
| author_sort | Mikkel Schou Andersen |
| collection | DOAJ |
| description | Abstract Meningiomas are the most common primary central nervous system tumor. Clinical trials have failed to support effective medical treatments, despite initially promising animal studies. A key issue could be that available experimental models fail to mimic the clinical situation. Hence, there is a need for meningioma models with high translational value for understanding pathophysiology and tests of possible medical treatments. Resemblance between models and clinical meningiomas should be optimized with respect to morphology, immunohistochemistry and epigenetic factors, which we aimed to do. Third passage primary patient-derived benign meningiomas were implanted intracranially in athymic nude rats. The animals were euthanized after three months. We found intra- and intertumoral variability in terms of tumor take rate (79.5% for superficially implanted cells and 25% for deeply implanted cells) and xenograft sizes. There were close resemblance between primary tumors and xenografts in morphology and immunohistochemistry. Furthermore, we performed DNA-methylation using the EPIC 850 K array on three pairs of primary tumors and xenografts. Copy number variation profiles and correlation plots on CpGs showed a high degree of similarities between primary tumors and corresponding xenografts. On differential methylation analysis, most probes were insignificant (866,074), 25 were hypermethylated, and 382 were hypomethylated, where no significant differentially methylated regions were revealed. |
| format | Article |
| id | doaj-art-28f1b85345624c69bf63dc8407bf978e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-28f1b85345624c69bf63dc8407bf978e2025-08-20T03:41:42ZengNature PortfolioScientific Reports2045-23222024-12-0114111610.1038/s41598-024-83456-7Orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumorsMikkel Schou Andersen0Bo Halle1Martin Wirenfeldt2Jeanette Krogh Petersen3Morten Winkler Møller4Philipp Jurmeister5Birgitte Brinkmann Olsen6Bjarne Winther Kristensen7Henning Boldt8Christian Bonde Pedersen9Tiit Mathiesen10Frantz Rom Poulsen11Department of Neurosurgery, Odense University HospitalDepartment of Neurosurgery, Odense University HospitalBRIDGE (Brain Research ‑ Inter Disciplinary Guided Excellence), University of Southern DenmarkDepartment of Pathology, Odense University HospitalDepartment of Neurosurgery, Odense University HospitalInstitute of Pathology, Ludwig Maximilians University Hospital MunichDepartment of Clinical Research, University of Southern DenmarkDepartment of Clinical Medicine and Biotech Research and Innovation Center (BRIC), University of CopenhagenDepartment of Clinical Research, University of Southern DenmarkDepartment of Neurosurgery, Odense University HospitalDepartment of Neurosurgery, Rigshospitalet, and Copenhagen UniversityDepartment of Neurosurgery, Odense University HospitalAbstract Meningiomas are the most common primary central nervous system tumor. Clinical trials have failed to support effective medical treatments, despite initially promising animal studies. A key issue could be that available experimental models fail to mimic the clinical situation. Hence, there is a need for meningioma models with high translational value for understanding pathophysiology and tests of possible medical treatments. Resemblance between models and clinical meningiomas should be optimized with respect to morphology, immunohistochemistry and epigenetic factors, which we aimed to do. Third passage primary patient-derived benign meningiomas were implanted intracranially in athymic nude rats. The animals were euthanized after three months. We found intra- and intertumoral variability in terms of tumor take rate (79.5% for superficially implanted cells and 25% for deeply implanted cells) and xenograft sizes. There were close resemblance between primary tumors and xenografts in morphology and immunohistochemistry. Furthermore, we performed DNA-methylation using the EPIC 850 K array on three pairs of primary tumors and xenografts. Copy number variation profiles and correlation plots on CpGs showed a high degree of similarities between primary tumors and corresponding xenografts. On differential methylation analysis, most probes were insignificant (866,074), 25 were hypermethylated, and 382 were hypomethylated, where no significant differentially methylated regions were revealed.https://doi.org/10.1038/s41598-024-83456-7MeningiomaXenograftOrthotopic tumor modelIn vivoDNA methylation profiling |
| spellingShingle | Mikkel Schou Andersen Bo Halle Martin Wirenfeldt Jeanette Krogh Petersen Morten Winkler Møller Philipp Jurmeister Birgitte Brinkmann Olsen Bjarne Winther Kristensen Henning Boldt Christian Bonde Pedersen Tiit Mathiesen Frantz Rom Poulsen Orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumors Scientific Reports Meningioma Xenograft Orthotopic tumor model In vivo DNA methylation profiling |
| title | Orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumors |
| title_full | Orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumors |
| title_fullStr | Orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumors |
| title_full_unstemmed | Orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumors |
| title_short | Orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumors |
| title_sort | orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient derived tumors |
| topic | Meningioma Xenograft Orthotopic tumor model In vivo DNA methylation profiling |
| url | https://doi.org/10.1038/s41598-024-83456-7 |
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