Article
Meningioma in vitro-xenograft model – The missing link between an in vitro and in vivo meningioma model
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Authors
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Jan Walter
- Klinik für Neurochirurgie, Universitätsklinikum Jena, Jena, Deutschland
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Diana Freitag
- Klinik für Neurochirurgie, Universitätsklinikum Jena, Jena, Deutschland
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Undine Tiller
- Klinik für Neurochirurgie, Universitätsklinikum Jena, Jena, Deutschland
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Rolf Kalff
- Klinik für Neurochirurgie, Universitätsklinikum Jena, Jena, Deutschland
| Published: | June 9, 2017 |
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Outline
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Objective: Therapeutic options for non-operable or recurrent meningiomas are infrequent. Therefore new strategies for treatment are required. For analysis of potential therapeutic agents numerous techniques are already available, like 2D- or 3D cell culture systems. A few meningioma mouse models have already been described, but none of them is really reproducible, because of the benign biological behavior of most meningiomas. Most of the commonly used in vitro models do not reflect the original cellular organization and heterogeneous structure of a tumor. Since a reliable alternative is still missing, this study aimed at establishing a well manageable method to generate human meningioma in a comparable tumor niche.
Methods: We generated 0.5cm organotypic brain slices of C57/BL6 mice and cultivated these under standard conditions for human meningioma cells for 24 hours. Then we engrafted 1x106 primary meningioma cells or a 2x2mm tissue fragment onto the slices. After cultivation for another 14 days, the slices were formalin fixed and cut into 10µm slices. Characterization of the engrafted cells or tissues was performed by hematoxylin and eosin staining as well as immunohistochemistry for EMA, Vimentin and Ki67.
Results: After cultivation we found “subjectively” growing and vital brain slices. Immunohistochemical analysis showed EMA-, Vimentin- and Ki67-postive cells. On the one hand we found tissue fragments as marker positive spots inside the mouse brain tissue. On the other hand after treatment with primary meningioma culture we found meningioma single cells migrated into the whole mouse brain slice.
Conclusion: We were able to co-cultivate human meningioma cells on and in mouse brain tissue slices in an in-vitro-xenograft model. The cultivated cells showed specific marker expression of meningioma tissue and were proliferative. In addition, the single cells showed a clear tendency for migratory behaviour. In summary, we established a well reproducible in-vitro-xenograft model as a preliminary stage for in vivo studies.
