Orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumors.

in Scientific reports by 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

TLDR

  • The study developed a patient-derived meningioma model with high translational value for understanding pathophysiology and testing medical treatments, and found close resemblance between primary tumors and xenografts in morphology and immunohistochemistry.

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.

Overview

  • The study aims to develop a meningioma model with high translational value for understanding pathophysiology and testing medical treatments.
  • Primary patient-derived benign meningiomas were implanted intracranially in athymic nude rats, and the animals were euthanized after three months.
  • The study aimed to optimize the resemblance between the models and clinical meningiomas with respect to morphology, immunohistochemistry, and epigenetic factors.

Comparative Analysis & Findings

  • The study found intra- and intertumoral variability in tumor take rate (79.5% for superficially implanted cells and 25% for deeply implanted cells) and xenograft sizes.
  • There was a close resemblance between primary tumors and xenografts in morphology and immunohistochemistry.
  • DNA-methylation analysis revealed a high degree of similarities between primary tumors and corresponding xenografts, with a few probes showing hypermethylation or hypomethylation.

Implications and Future Directions

  • The study's findings demonstrate the potential of using patient-derived meningioma models for understanding pathophysiology and testing medical treatments.
  • Future studies could focus on optimizing the models to better mimic the clinical situation and addressing the limitations of animal models for meningioma research.
  • Epigenetic analysis could be used to identify specific biomarkers for meningioma diagnosis and treatment monitoring.
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