PhD Scientific Days 2024

Pathological and Oncological Sciences II.

Organoids in Research Against Glioblastoma

Text of the abstract

Introduction:
The most common primary intracranial malignant tumor in adults is glioblastoma, which is a very aggressive and invasive tumor. Its high lethality makes the development of new therapies and study models very important. Currently, the use of animals in research is still essential to understand biological processes, diseases, and the development of new therapies. Genetically modified mouse models and xerografts of tumor material derived from patients are used to study glioblastoma. The use of these animals has many ethical and legal implications, making it essential to search for alternatives.
Aims:
We propose an alternative based on organoids, 3D models that reproduce the characteristics of the tissue, allowing us to reduce the use of animals. These models are more manageable compared to in vivo models. Our objective in this project is the development of organoids for the study of gliomagenesis and their application in the discovery of new therapies.
Methods:
We start from a monolayer culture of several cell lines (U-87 MG, T731 MG and C-19MG), which induce the formation of neurospheres, neural differentiation and the formation of organoids.
Results:
Our results show that both cells of human and murine origin have the capacity to form organoids, showing growth differences between lines, reproducing the behaviour they have when they are cultured in monolayer. The tests carried out show cells of different sizes and morphologies, with greater cell density in the periphery. There is expression of glial, neuronal and dedifferentiation lineage markers, so there are phenotypic changes with respect to the initial cells due to dedifferentiation processes and subsequently differentiation and structuring.
Conclusion:
These results demonstrate the ability to obtain a 3D model of these cell lines that reproduces the tissue that cells form in the body, allowing their study and understanding for the development of new therapies, as well as their use to test new drugs. This allows the number of animals used in later stages to be reduced, thus reducing ethical and legal implications.
Funding:
This work has been funded by the Spanish Research Agency,the Department of Culture, Education and University Planning, Xunta de Galicia and the European Union.