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A perfused multi-well bioreactor platform to assess tumor organoid response to a chemotherapeutic gradient
There is an urgent need to develop new therapies for colorectal cancer that has metastasized to the liver and, more fundamentally, to develop improved preclinical platforms of colorectal cancer liver metastases (CRCLM) to screen therapies for efficacy. To this end, we developed a multi-well perfusab...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264793/ https://www.ncbi.nlm.nih.gov/pubmed/37324446 http://dx.doi.org/10.3389/fbioe.2023.1193430 |
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author | Wasson, Elisa Marie He, Wei Ahlquist, Jesse Hynes, William Fredrick Triplett, Michael Gregory Hinckley, Aubree Karelehto, Eveliina Gray-Sherr, Delaney Ruth Friedman, Caleb Fisher Robertson, Claire Shusteff, Maxim Warren, Robert Coleman, Matthew A. Moya, Monica Lizet Wheeler, Elizabeth K. |
author_facet | Wasson, Elisa Marie He, Wei Ahlquist, Jesse Hynes, William Fredrick Triplett, Michael Gregory Hinckley, Aubree Karelehto, Eveliina Gray-Sherr, Delaney Ruth Friedman, Caleb Fisher Robertson, Claire Shusteff, Maxim Warren, Robert Coleman, Matthew A. Moya, Monica Lizet Wheeler, Elizabeth K. |
author_sort | Wasson, Elisa Marie |
collection | PubMed |
description | There is an urgent need to develop new therapies for colorectal cancer that has metastasized to the liver and, more fundamentally, to develop improved preclinical platforms of colorectal cancer liver metastases (CRCLM) to screen therapies for efficacy. To this end, we developed a multi-well perfusable bioreactor capable of monitoring CRCLM patient-derived organoid response to a chemotherapeutic gradient. CRCLM patient-derived organoids were cultured in the multi-well bioreactor for 7 days and the subsequently established gradient in 5-fluorouracil (5-FU) concentration resulted in a lower IC(50) in the region near the perfusion channel versus the region far from the channel. We compared behaviour of organoids in this platform to two commonly used PDO culture models: organoids in media and organoids in a static (no perfusion) hydrogel. The bioreactor IC(50) values were significantly higher than IC(50) values for organoids cultured in media whereas only the IC(50) for organoids far from the channel were significantly different than organoids cultured in the static hydrogel condition. Using finite element simulations, we showed that the total dose delivered, calculated using area under the curve (AUC) was similar between platforms, however normalized viability was lower for the organoid in media condition than in the static gel and bioreactor. Our results highlight the utility of our multi-well bioreactor for studying organoid response to chemical gradients and demonstrate that comparing drug response across these different platforms is nontrivial. |
format | Online Article Text |
id | pubmed-10264793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102647932023-06-15 A perfused multi-well bioreactor platform to assess tumor organoid response to a chemotherapeutic gradient Wasson, Elisa Marie He, Wei Ahlquist, Jesse Hynes, William Fredrick Triplett, Michael Gregory Hinckley, Aubree Karelehto, Eveliina Gray-Sherr, Delaney Ruth Friedman, Caleb Fisher Robertson, Claire Shusteff, Maxim Warren, Robert Coleman, Matthew A. Moya, Monica Lizet Wheeler, Elizabeth K. Front Bioeng Biotechnol Bioengineering and Biotechnology There is an urgent need to develop new therapies for colorectal cancer that has metastasized to the liver and, more fundamentally, to develop improved preclinical platforms of colorectal cancer liver metastases (CRCLM) to screen therapies for efficacy. To this end, we developed a multi-well perfusable bioreactor capable of monitoring CRCLM patient-derived organoid response to a chemotherapeutic gradient. CRCLM patient-derived organoids were cultured in the multi-well bioreactor for 7 days and the subsequently established gradient in 5-fluorouracil (5-FU) concentration resulted in a lower IC(50) in the region near the perfusion channel versus the region far from the channel. We compared behaviour of organoids in this platform to two commonly used PDO culture models: organoids in media and organoids in a static (no perfusion) hydrogel. The bioreactor IC(50) values were significantly higher than IC(50) values for organoids cultured in media whereas only the IC(50) for organoids far from the channel were significantly different than organoids cultured in the static hydrogel condition. Using finite element simulations, we showed that the total dose delivered, calculated using area under the curve (AUC) was similar between platforms, however normalized viability was lower for the organoid in media condition than in the static gel and bioreactor. Our results highlight the utility of our multi-well bioreactor for studying organoid response to chemical gradients and demonstrate that comparing drug response across these different platforms is nontrivial. Frontiers Media S.A. 2023-05-31 /pmc/articles/PMC10264793/ /pubmed/37324446 http://dx.doi.org/10.3389/fbioe.2023.1193430 Text en Copyright © 2023 Wasson, He, Ahlquist, Hynes, Triplett, Hinckley, Karelehto, Gray-Sherr, Friedman, Robertson, Shusteff, Warren, Coleman, Moya and Wheeler. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology Wasson, Elisa Marie He, Wei Ahlquist, Jesse Hynes, William Fredrick Triplett, Michael Gregory Hinckley, Aubree Karelehto, Eveliina Gray-Sherr, Delaney Ruth Friedman, Caleb Fisher Robertson, Claire Shusteff, Maxim Warren, Robert Coleman, Matthew A. Moya, Monica Lizet Wheeler, Elizabeth K. A perfused multi-well bioreactor platform to assess tumor organoid response to a chemotherapeutic gradient |
title | A perfused multi-well bioreactor platform to assess tumor organoid response to a chemotherapeutic gradient |
title_full | A perfused multi-well bioreactor platform to assess tumor organoid response to a chemotherapeutic gradient |
title_fullStr | A perfused multi-well bioreactor platform to assess tumor organoid response to a chemotherapeutic gradient |
title_full_unstemmed | A perfused multi-well bioreactor platform to assess tumor organoid response to a chemotherapeutic gradient |
title_short | A perfused multi-well bioreactor platform to assess tumor organoid response to a chemotherapeutic gradient |
title_sort | perfused multi-well bioreactor platform to assess tumor organoid response to a chemotherapeutic gradient |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264793/ https://www.ncbi.nlm.nih.gov/pubmed/37324446 http://dx.doi.org/10.3389/fbioe.2023.1193430 |
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