Ex Vivo Modeling of Human Neuroendocrine Tumors in Tissue Surrogates

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 conclus...

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Main Authors: Brendon Herring, Samuel Jang, Jason Whitt, Kayla Goliwas, Zviadi Aburjania, Vikas Dudeja, Bin Ren, Joel Berry, James Bibb, Andra Frost, Herbert Chen, John Bart Rose, Renata Jaskula-Sztul
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-12-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2021.710009/full
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author Brendon Herring
Samuel Jang
Jason Whitt
Kayla Goliwas
Zviadi Aburjania
Vikas Dudeja
Bin Ren
Joel Berry
James Bibb
Andra Frost
Herbert Chen
John Bart Rose
Renata Jaskula-Sztul
author_facet Brendon Herring
Samuel Jang
Jason Whitt
Kayla Goliwas
Zviadi Aburjania
Vikas Dudeja
Bin Ren
Joel Berry
James Bibb
Andra Frost
Herbert Chen
John Bart Rose
Renata Jaskula-Sztul
author_sort Brendon Herring
collection DOAJ
description 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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spelling doaj.art-0d1fc72d7b6149aab94366fba685e6972022-12-21T18:45:38ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-12-011210.3389/fendo.2021.710009710009Ex Vivo Modeling of Human Neuroendocrine Tumors in Tissue SurrogatesBrendon Herring0Samuel Jang1Jason Whitt2Kayla Goliwas3Zviadi Aburjania4Vikas Dudeja5Bin Ren6Joel Berry7James Bibb8Andra Frost9Herbert Chen10John Bart Rose11Renata Jaskula-Sztul12Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesFew 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.https://www.frontiersin.org/articles/10.3389/fendo.2021.710009/fullneuroendocrine tumorbioreactor 3D culturebiomedical engineering (BME)tumor surrogatestumor modeling
spellingShingle Brendon Herring
Samuel Jang
Jason Whitt
Kayla Goliwas
Zviadi Aburjania
Vikas Dudeja
Bin Ren
Joel Berry
James Bibb
Andra Frost
Herbert Chen
John Bart Rose
Renata Jaskula-Sztul
Ex Vivo Modeling of Human Neuroendocrine Tumors in Tissue Surrogates
Frontiers in Endocrinology
neuroendocrine tumor
bioreactor 3D culture
biomedical engineering (BME)
tumor surrogates
tumor modeling
title Ex Vivo Modeling of Human Neuroendocrine Tumors in Tissue Surrogates
title_full Ex Vivo Modeling of Human Neuroendocrine Tumors in Tissue Surrogates
title_fullStr Ex Vivo Modeling of Human Neuroendocrine Tumors in Tissue Surrogates
title_full_unstemmed Ex Vivo Modeling of Human Neuroendocrine Tumors in Tissue Surrogates
title_short Ex Vivo Modeling of Human Neuroendocrine Tumors in Tissue Surrogates
title_sort ex vivo modeling of human neuroendocrine tumors in tissue surrogates
topic neuroendocrine tumor
bioreactor 3D culture
biomedical engineering (BME)
tumor surrogates
tumor modeling
url https://www.frontiersin.org/articles/10.3389/fendo.2021.710009/full
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