Cell Culture Models for Translational Research on Thymomas and Thymic Carcinomas: Current Status and Future Perspectives

Abstract

Cell culture model systems are fundamental tools for studying cancer biology and identifying therapeutic vulnerabilities in a controlled environment. TET cells are notoriously difficult to culture, with only a few permanent cell lines available. The optimal conditions and requirements for the ex vivo establishment and permanent expansion of TET cells have not been systematically studied, and it is currently unknown whether different TET subtypes require different culture conditions or specific supplements. The few permanent cell lines available represent only type AB thymomas and thymic carcinomas, while attempts to propagate tumor cells derived from type B thymomas so far have been frustrated. It is conceivable that epithelial cells in type B thymomas are critically dependent on their interaction with immature T cells or their three-dimensional scaffold. Extensive studies leading to validated cell culture protocols would be highly desirable and a major advance in the field. Alternative methods such as tumor cell organoid models, patient-derived xenografts, or tissue slices have been sporadically used in TETs, but their specific contributions and advantages remain to be shown.

Keywords: molecular mechanisms; patient-derived cell culture; personalized medicine; targeted therapies; thymic epithelial tumors.

Figure 1

Shallow whole-genome sequencing and multi-color FISH analysis of T1889 cells showing a highly aberrant karyotype (courtesy of Dr. Katayoon Shirneshan, University Medical Center Göttingen). Multi-color FISH can be used to trace the exchange of large portions of genomic material across different chromosomes (for example, note the translocation of large parts of the long arm of chr. 4 (bright green) to one of the two chromosomes 1).

Figure 2

Patient-derived primary cell culture of type AB thymoma. (A) Whole-tissue single-cell suspensions 4 days after isolation show varying cell morphologies. (B) Elongated spindle cells prevail after 3 weeks and thereafter (C).

Figure 3

Representative images of a matrix-embedded, patient-derived 3D thymoma organoid model. (A) Original tumor (HE, ×200), (B) Tumor-derived organoids (overview, HE, ×100) (C) detail of (B) (HE, ×250), (D) keratin 19 staining (immunohistochemistry, ×250).

Figure 4

Automated workflow for optimization of comprehensive drug testing of TET cells (created with https://BioRender.com).