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Author
Fallon Estaún, Inés
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Abstract
The conventional in vitro monolayer cultures are very standardized through the scientific community and the screening assays, but they often produce results that are not representative of in vivo response. A major percentage of the drugs that do not succeed in clinical development are associated to lack of efficacy or safety. Recently, to overcome this limitation, novel three-dimensional cell culture systems have gained increasing interest in drug discovery due to their evident advantages in providing a more physiologically relevant and more predictive models.
Medulloblastoma is the most frequent occurring brain tumour in childhood. It exhibits a high molecular heterogenicity presenting four subtypes depending on the genetic driving mutations: WNT-activated, SHH-activated, Group 3 and Group 4. Group 3 carries the worst prognosis of all, represents 25% of all patients. Its poor prognosis is related to MYC amplification and is the most likely subgroup to present with metastatic dissemination. Current treatments, despite the last decade improvements, still show limited success: 40% of patients will not survive. And the surviving patients present serious long-term side effects. Overall, demonstrating the need to find directed treatments for this disease with greater therapeutic effect and lower toxicity.
With this project we aim to develop an in vitro predictive model to test and assess efficacy and toxicity of potential new treatments against Group 3 medulloblastoma: a new model based in 3D culturing systems using scaffolds that mimic the brain extracellular matrix.
Steps towards the development of a co-culture model of Group 3 medulloblastoma D341 cell line with brain cells as control cells, representing surrounding tumour’s tissue, have been performed.
In the first place, we have selected and developed a control cell line representative of brain cells to assess toxicity of potential treatments. Secondly, a scaffold representative of brain extracellular matrix has been selected and 3D culture systems have been developed for Group 3 medulloblastoma. Finally, first steps in the development of co-cultures have been achieved, such as labelling two cell populations with fluorescent dyes.
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