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Establishment of patient-derived organoid models of lower-grade glioma

BACKGROUND: Historically, creating patient-derived models of lower-grade glioma (LGG) has been challenging, contributing to few experimental platforms that support laboratory-based investigations of this disease. Although organoid modeling approaches have recently been employed to create in vitro mo...

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Autores principales: Abdullah, Kalil G, Bird, Cylaina E, Buehler, Joseph D, Gattie, Lauren C, Savani, Milan R, Sternisha, Alex C, Xiao, Yi, Levitt, Michael M, Hicks, William H, Li, Wenhao, Ramirez, Denise M O, Patel, Toral, Garzon-Muvdi, Tomas, Barnett, Samuel, Zhang, Gao, Ashley, David M, Hatanpaa, Kimmo J, Richardson, Timothy E, McBrayer, Samuel K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8972292/
https://www.ncbi.nlm.nih.gov/pubmed/34850183
http://dx.doi.org/10.1093/neuonc/noab273
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author Abdullah, Kalil G
Bird, Cylaina E
Buehler, Joseph D
Gattie, Lauren C
Savani, Milan R
Sternisha, Alex C
Xiao, Yi
Levitt, Michael M
Hicks, William H
Li, Wenhao
Ramirez, Denise M O
Patel, Toral
Garzon-Muvdi, Tomas
Barnett, Samuel
Zhang, Gao
Ashley, David M
Hatanpaa, Kimmo J
Richardson, Timothy E
McBrayer, Samuel K
author_facet Abdullah, Kalil G
Bird, Cylaina E
Buehler, Joseph D
Gattie, Lauren C
Savani, Milan R
Sternisha, Alex C
Xiao, Yi
Levitt, Michael M
Hicks, William H
Li, Wenhao
Ramirez, Denise M O
Patel, Toral
Garzon-Muvdi, Tomas
Barnett, Samuel
Zhang, Gao
Ashley, David M
Hatanpaa, Kimmo J
Richardson, Timothy E
McBrayer, Samuel K
author_sort Abdullah, Kalil G
collection PubMed
description BACKGROUND: Historically, creating patient-derived models of lower-grade glioma (LGG) has been challenging, contributing to few experimental platforms that support laboratory-based investigations of this disease. Although organoid modeling approaches have recently been employed to create in vitro models of high-grade glioma (HGG), it is unknown whether this approach can be successfully applied to LGG. METHODS: In this study, we developed an optimized protocol for the establishment of organoids from LGG primary tissue samples by utilizing physiologic (5%) oxygenation conditions and employed it to produce the first known suite of these models. To assess their fidelity, we surveyed key biological features of patient-derived organoids using metabolic, genomic, histologic, and lineage marker gene expression assays. RESULTS: Organoid models were created with a success rate of 91% (n = 20/22) from primary tumor samples across glioma histological subtypes and tumor grades (WHO Grades 1–4), and a success rate of 87% (13/15) for WHO Grade 1–3 tumors. Patient-derived organoids recapitulated stemness, proliferative, and tumor-stromal composition profiles of their respective parental tumor specimens. Cytoarchitectural, mutational, and metabolic traits of parental tumors were also conserved. Importantly, LGG organoids were maintained in vitro for weeks to months and reanimated after biobanking without loss of integrity. CONCLUSIONS: We report an efficient method for producing faithful in vitro models of LGG. New experimental platforms generated through this approach are well positioned to support preclinical studies of this disease, particularly those related to tumor immunology, tumor-stroma interactions, identification of novel drug targets, and personalized assessments of treatment response profiles.
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spelling pubmed-89722922022-04-01 Establishment of patient-derived organoid models of lower-grade glioma Abdullah, Kalil G Bird, Cylaina E Buehler, Joseph D Gattie, Lauren C Savani, Milan R Sternisha, Alex C Xiao, Yi Levitt, Michael M Hicks, William H Li, Wenhao Ramirez, Denise M O Patel, Toral Garzon-Muvdi, Tomas Barnett, Samuel Zhang, Gao Ashley, David M Hatanpaa, Kimmo J Richardson, Timothy E McBrayer, Samuel K Neuro Oncol Basic and Translational Investigations BACKGROUND: Historically, creating patient-derived models of lower-grade glioma (LGG) has been challenging, contributing to few experimental platforms that support laboratory-based investigations of this disease. Although organoid modeling approaches have recently been employed to create in vitro models of high-grade glioma (HGG), it is unknown whether this approach can be successfully applied to LGG. METHODS: In this study, we developed an optimized protocol for the establishment of organoids from LGG primary tissue samples by utilizing physiologic (5%) oxygenation conditions and employed it to produce the first known suite of these models. To assess their fidelity, we surveyed key biological features of patient-derived organoids using metabolic, genomic, histologic, and lineage marker gene expression assays. RESULTS: Organoid models were created with a success rate of 91% (n = 20/22) from primary tumor samples across glioma histological subtypes and tumor grades (WHO Grades 1–4), and a success rate of 87% (13/15) for WHO Grade 1–3 tumors. Patient-derived organoids recapitulated stemness, proliferative, and tumor-stromal composition profiles of their respective parental tumor specimens. Cytoarchitectural, mutational, and metabolic traits of parental tumors were also conserved. Importantly, LGG organoids were maintained in vitro for weeks to months and reanimated after biobanking without loss of integrity. CONCLUSIONS: We report an efficient method for producing faithful in vitro models of LGG. New experimental platforms generated through this approach are well positioned to support preclinical studies of this disease, particularly those related to tumor immunology, tumor-stroma interactions, identification of novel drug targets, and personalized assessments of treatment response profiles. Oxford University Press 2021-11-26 /pmc/articles/PMC8972292/ /pubmed/34850183 http://dx.doi.org/10.1093/neuonc/noab273 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Basic and Translational Investigations
Abdullah, Kalil G
Bird, Cylaina E
Buehler, Joseph D
Gattie, Lauren C
Savani, Milan R
Sternisha, Alex C
Xiao, Yi
Levitt, Michael M
Hicks, William H
Li, Wenhao
Ramirez, Denise M O
Patel, Toral
Garzon-Muvdi, Tomas
Barnett, Samuel
Zhang, Gao
Ashley, David M
Hatanpaa, Kimmo J
Richardson, Timothy E
McBrayer, Samuel K
Establishment of patient-derived organoid models of lower-grade glioma
title Establishment of patient-derived organoid models of lower-grade glioma
title_full Establishment of patient-derived organoid models of lower-grade glioma
title_fullStr Establishment of patient-derived organoid models of lower-grade glioma
title_full_unstemmed Establishment of patient-derived organoid models of lower-grade glioma
title_short Establishment of patient-derived organoid models of lower-grade glioma
title_sort establishment of patient-derived organoid models of lower-grade glioma
topic Basic and Translational Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8972292/
https://www.ncbi.nlm.nih.gov/pubmed/34850183
http://dx.doi.org/10.1093/neuonc/noab273
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