4.7 Article

Ex Vivo Modeling of Human Neuroendocrine Tumors in Tissue Surrogates

Journal

FRONTIERS IN ENDOCRINOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2021.710009

Keywords

neuroendocrine tumor; bioreactor 3D culture; biomedical engineering (BME); tumor surrogates; tumor modeling

Funding

  1. North American Neuroendocrine Tumor Society Basic/Translational Science Investigator Grant
  2. Central Surgical Association Enrichment Award
  3. UAB Center for Clinical and Translational Sciences Training Grant [TL1 TR001418]
  4. National Cancer Institute of the National Institutes of Health [K08CA234209, R21CA226491-01A1]
  5. UAB Medical Scientist Training Program [T32 GM008361]
  6. NCI Cancer Center Support Grant [P30 CA013148, NIH P30 AR048311, P30 AI27667]

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This study proposes the use of an ex vivo 3D flow-perfusion bioreactor system for cultivating and studying patient-derived neuroendocrine tumors (NETs), demonstrating its utility and providing methods for evaluating therapeutic efficacy. The research suggests that the bioreactor system and similar 3D culture models may be valuable tools for culturing patient-derived NETs and monitoring their response to therapy ex vivo.
Few models exist for studying neuroendocrine tumors (NETs), and there are mounting concerns that the currently available array of cell lines is not representative of NET biology. The lack of stable patient-derived NET xenograft models further limits the scientific community's ability to make conclusions about NETs and their response to therapy in patients. To address these limitations, we propose the use of an ex vivo 3D flow-perfusion bioreactor system for culturing and studying patient-derived NET surrogates. Herein, we demonstrate the utility of the bioreactor system for culturing NET surrogates and provide methods for evaluating the efficacy of therapeutic agents on human NET cell line xenograft constructs and patient-derived NET surrogates. We also demonstrate that patient-derived NET tissues can be propagated using the bioreactor system and investigate the near-infrared (NIR) dye IR-783 for its use in monitoring their status within the bioreactor. The results indicate that the bioreactor system and similar 3D culture models may be valuable tools for culturing patient-derived NETs and monitoring their response to therapy ex vivo.

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