A Murine Model of Glioblastoma Initiating Cells and Human Brain Organoid Xenograft for Photodynamic Therapy Testing

ABSTRACT: Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. As recurrence in glioblastoma is locally generated around the resection cavity, the ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic and microenvironmental properties of neural tissues. Photodynamic therapy (PDT) relies on photo-toxic effects induced by specific molecules (photosensitisers) upon absorption of photons from a light source. Such toxic effects are not specific to a particular molecular fingerprint of GBM, but rather depend on selective accumulation of the photosensitiser inside tumour cells and their sensitivity to the effects, triggered by light. Here we report four new GICs obtained in Hospital Clinic Barcelona, HCB-GICs, to optimize preclinical studies of PDT, and to explore neoadjuvant protocols for a more effective PDT and photodiagnostic visualization. HCB-GIC cells express the known “stemness” markers Nestin and SOX2, Vimentin and CD44, contributing to invasiveness and to infiltrative ability within brain organoids, properties associated also to mesenchymal phenotype. HCB-GICs are susceptible to be treated with PDT, since the burden of cells into organoids decreased while increased cell death after irradiation. Moreover, we optimize an experimental in vivo model, able to assess the antitumoral effect of 5-ALA mediated PDT in engraftments of HCB-GICs co-cultures on the kidneys of high immunosupressed mice. In conclusion, we suggest that PDT might be an effective therapy to kill GICs with heterogeneous molecular fingerprint that achieve high levels of PPIX accumulation in tumor niche.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279049 | GEO | 2025/09/29

REPOSITORIES: GEO