Creating bespoke functionalised peptide gels to model the brain tumour microenvironment

Lead Research Organisation: University of Nottingham
Department Name: School of Medicine

Abstract

Introduction
Current in vitro models used to study children's brain cancer typically fail to recapitulate the complexity of the brain tumour microenvironment. 2D monolayer cultures, or 3D models containing animal-derived products, unreliably represent human extracellular matrices (ECM), and raise ethical questions of using animal-derived products in research. Therefore, we aim to optimise a synthetic peptide gel model which can be selectively functionalised with various ECM components to mimic specific tumour microenvironments.
Materials and Methods
The self-assembling FEFEFKFK gelator octapeptide has been used to encapsulate a variety of cell types with excellent viability. Functionalisation of the gel can be achieved by entrapment of soluble ECM components during cell encapsulation or by covalent modification of the gelator peptide. Mouse embryonic stem (mES) cells have been used as a tool for detecting the biological impact of using specific glycosaminoglycans to functionalise the gels.
Results
mES cells grown in the peptide gels can be induced to differentiate in serum free culture. We have previously demonstrated that the glycosaminoglycan heparan sulphate (HS) is essential for mES cell differentiation to the neural lineage. Using mES cells deficient in HS synthesis we can probe the ability of exogenous HS, added in to the gel, to support differentiation. This provides a sensitive and relevant read-out for functionalisation with biologically active ECM components.
Discussion
Initial results demonstrate that cell types relevant to childhood brain tumours can be cultured in the peptide gels. Functionalisation of the gel was found to drive characteristic changes in the behaviour of at least one cell type. We have constructed a test environment to evaluate the biological effect of modifications to the hydrogel. Our aim is to develop a model that recapitulates the brain tumour microenvironment to improve upon current models, without the need for animal-derived products and their associated variability.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M008770/1 01/10/2015 30/09/2023
1943897 Studentship BB/M008770/1 01/10/2017 30/09/2021 Johnathan Curd