Establishment of a patient-derived 3D in vitro meningioma model in xeno-free hydrogel for clinical applications

Document Type

Article

Publication Date

4-24-2025

Publication Title

Acta Neuropathol Commun

Abstract

BACKGROUND: Meningiomas exhibit a complex biology that, despite notable successes in preclinical studies, contributes to the failures of pharmaceutical clinical trials. Animal models using patient tumor cells closely mimic in vivo conditions but are labor-intensive, costly, and unsuitable for high-throughput pharmaceutical testing. In comparison, monolayer cell models (two-dimensional, 2D) are cost-efficient but lack primary tumor cell-cell interactions, potentially overestimating treatment effects. Three-dimensional (3D) models offer an alternative through more precise mimicking of tumor morphology and physiology than 2D models and are less costly than in vivo methods. Here, we aimed to establish a 3D cell model in a solid xeno-free medium using patient-derived tumors, thus creating a bench-to-clinic pathway for personalized pharmaceutical testing.

METHODS: Four WHO grade 1 and one WHO grade 2 (third-passage, fresh) and 12 WHO grade 1 patient-derived meningioma cells (sixth-passage, frozen) and the malignant IOMM-Lee cell line were used to establish 2D and 3D models. The 3D model was developed using a solid xeno-free medium. After 3 months for the primary tumor and 13 days for the IOMM-Lee cell line, the 3D models were extracted and assessed using histology, immunohistochemistry, and epigenetic analyses (EPICv2 array) on five pairs to evaluate their structural fidelity, cellular composition, and epigenetic landscape compared to the original tumor.

RESULTS: None of the frozen samples successfully generated 3D models. Models from fresh meningioma samples were more immunohistochemically similar to the primary tumors compared to 2D models, particularly regarding proliferation. 3D models displayed loss of fibrous tissue. All 3D models had similar copy number variation profiles, visually. Genome-wide DNA methylation level patterns were similar between pairs of 3D models and primary tumors. Correlation plots between CpG methylation levels showed high congruency between primary meningiomas and their corresponding 3D models for all samples (R > 0.95).

CONCLUSIONS: Our patient-derived 3D meningioma models closely mimicked primary tumors in terms of cell morphology, immunohistochemical markers and genome-wide DNA methylation patterns, providing a cost-effective and accessible alternative to in vivo models. This approach has the potential to facilitate personalized treatment strategies for patients requiring additional therapy beyond surgery.

Medical Subject Headings

Meningioma; Humans; Meningeal Neoplasms; Hydrogels; Cell Line, Tumor; Female; Cell Culture Techniques, Three Dimensional; Cell Culture Techniques; Male; Middle Aged

PubMed ID

40269981

Volume

13

Issue

1

First Page

81

Last Page

81

Find It @ Sladen

Share

COinS