Artikel
An orthotopic xenograft mouse model for benign human meningiomas
Ein orthotopes Xenograft-Mausmodell für benigne humane Meningeome
Suche in Medline nach
Autoren
-
Diana Freitag
- Universitätsklinikum Jena, Klinik für Neurochirurgie, Jena, Deutschland
-
Karl-Heinz Herrmann
- Universitätsklinikum Jena, Institut für Diagnostische und Interventionelle Radiologie, Jena, Deutschland
-
Jürgen R. Reichenbach
- Universitätsklinikum Jena, Institut für Diagnostische und Interventionelle Radiologie, Jena, Deutschland
-
Christian Ewald
- Städtisches Klinikum Brandenburg, Klinik für Neurochirurgie, Brandenburg an der Havel, Deutschland
-
Rolf Kalff
- Universitätsklinikum Jena, Klinik für Neurochirurgie, Jena, Deutschland
-
Jan Walter
- Universitätsklinikum Jena, Klinik für Neurochirurgie, Jena, Deutschland; Klinikum Saarbrücken, Klinik für Neurochirurgie, Saarbrücken, Deutschland
| Veröffentlicht: | 26. Juni 2020 |
|---|
Gliederung
Text
Objective: Low-grade meningiomas are mainly characterized by their benign biological behavior, slow growth and low metabolic rates. Since the usual properties of malignant tumors, such as uncontrolled growth, tendency to migrate or infiltration, are therefore not usable, research on this tumor entity is particularly difficult. A reliable in vivo model close to the patient is still missing. The aim of this study was to develop a functioning orthotopic xenograft model for human WHO°I meningiomas.
Methods: Fifteen 10-12 weeks old female NOD.SCID mice were subdurally injected with a suspension of 1x106 cells. Cells of various differentiation levels were:
- 1.
- primary meningioma cells (PMCs) (differentiated, p1),
- 2.
- PMCs and 30% freshly isolated meningioma stem cells (MSCs) and
- 3.
- PMCs and 70% MSCs.
Throughout the experiment, the animals were examined for general condition, weight and abnormalities. 2, 12 and 24 weeks follow-up controls were performed using 9.7T small MRI. The used MRI sequences were a T2-weighted spinecho, a T1-weighted 3D FLASH sequence both native and post contrast agent (100µl Gadovist, diluted 1:10). Since meningiomas often consist of very hard, dura-mater like tissue we used an additional T1-weigted UTE sequence post contrast to ensure that short T2 tissue will be visible. Based on the image data, the volumes of the contrast-enriching areas were calculated. After 24 weeks, the tissue was prepared and analyzed.
Results: The imaging showed that in the T1-weighted sequences after contrast agent (CA) administration in group 1 only very small or no CA-accumulating areas could be detected. We detected an increasing CA-enriching signal only in 1 animal of group 1. In contrast, both group 2 showed a strong tendency (p=0.051) and group 3 even a significant (p=0.024) volume increase of the CA-enriching areas after 24 weeks. The analysis of mortality rates showed a high mortality in group 3.
Conclusion: On the basis of the data, it can be clearly stated that it is possible to induce a meningioma in mice, with the help of meningioma stem cells. Thus, we were able to develop an orthotopic xenograft model for benign human meningiomas, which is now available for further applications.
