Development of a 3D patient-derived extracellular matrix hydrogel model of small intestinal neuroendocrine tumour and mesenteric fibrosis

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Introduction: The pathogenesis of mesenteric fibrosis in small intestinal neuroendocrine tumours (SI-NETs) is poorly understood, limiting development of effective treatments and biomarkers. A major barrier to research is the lack of disease models.

Aim(s): This project seeks to develop a novel 3D model of SI-NET and SI-NET–induced fibrosis to enhance our understanding of mesenteric fibrosis.

Materials and methods: Healthy small intestine and mesenteric metastases from SI-NET patients were collected and decellularised. Decellularised tissue was lyophilised and solubilised to create extracellular matrix (ECM) hydrogels. Primary fibroblasts from normal small intestine, primary tumour, normal mesentery, and mesenteric metastases of SI-NET patients were isolated and cultured in the ECM hydrogels as a monoculture or cocultured with SI-NET spheroids (GOT1 cell line) and assessed for differences in viability and gene expression. The gels were treated with TGFβ and analysed using PrestoBlue assay, immunohistochemistry, and RT-qPCR.

Conference:

Presenting Author:

Authors: Hodgetts H, Martins M, Luong T, Hall A, Webster A,

Keywords: small intestine, neuroendocrine, 3D model, hydrogel, fibrosis,