Phd in INNOVATIVE TECHNOLOGIES IN DISEASES OF
SKELETON, SKIN AND ORO-CRANIOFACIAL DISTRICT

Thesis title: Organoidi tumorali derivati da paziente (PDOs): nuovo strumento di rappresentazione istologica e molecolare dei tumori cerebrali

Introduction: The lack of an appropriate model to mimic the characteristics of brain tumors has led to the creation of organoids: three-dimensional cell aggregates derived from tumor cells that mimic the tissue of origin within an original cellular microenvironment and with a rapid generation time. Materials and methods: Tumor fragments were collected and used to generate 42 organoids from IDH WILD TYPE and IDH MUTANT lesions. Seventeen organoids derived from meningiomas were also generated. Phenotypic and molecular analyses were performed to evaluate the ability to reproduce these characteristics in vitro. The degree of expression conservation and the dynamics of specific molecular markers in the organoids were also evaluated in comparison with the original tumor tissue. Results: PDOS obtained from GBMs showed higher success rates than samples from IDH1-mutated gliomas. The survival and proliferation of cultures derived from GBMs were higher than those obtained from IDH1-mutated gliomas; this correlates with the proliferation rate of the original tumor.The morphology of the organoids faithfully reproduced that of the original tumor, highlighting histological characteristics consistent with the same tumor subtype; the markers were also expressed in a manner consistent with that observed in the original tissues. Furthermore, expression remained stable over time, underscoring the robustness of the model. Conclusions: The study showed that the creation of PDOs provides highly representative in vitro models of the original tumor, both histologically and molecularly. This allows for exploration of their potential use as a functional validation tool and for preclinical studies.