Development of a Personalized Human Immunocompetent Ex-Vivo Model of Neuroendocrine Liver Metastasis Using Precision Cut Tissue Slice Technology


Introduction: Liver metastasis (LM) are very frequent (65-95%) and represent a crucial prognostic factor in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP NENs). The paucity of relevant experimental models has limited the understanding of the pathophysiology of NENs and the development of efficient therapeutic strategies

Aim(s): The aim of this study is to utilise the precision cut tissue slice (PCTS) technology to develop an immunocompetent model of LM-NENs to test new therapeutics and elucidate immunological, molecular and cellular characteristics.

Materials and methods: To date, 20 patients have been consented and 6 liver samples collected. Peripheral blood mononuclear cells have been isolated from all patients and will be used for further analysis. PCTS from LM-NENs and corresponding surrounding tissue were cultured for up to 15 days. Viability was assessed over culture by histology, lactate dehydrogenase release in the supernatant and ATP content in the tissue. Cell death/apoptosis were assessed measuring cytokeratin 18. Proliferation (Ki67) and Chromogranin A was evaluated by immunofluorescence. Infiltrating immune cells were characterised using PCR microarray analysis.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Doornebal E

Authors: Doornebal E, Harris N, Miquel R, Zen Y, Pizanias M,

Keywords: Liver, neuroendocrine liver metastasis, ex-vivo model, personalized medicine, immunocompetent, organotypic tissue slices,

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