Synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas

Abstract Background. Pediatric gliomas comprise a diverse set of brain tumor entities that have substantial long-term ramifications for patient survival and quality of life. However, the study of these tumors is currently limited due to a lack of authentic models. Additionally, many aspects of pe...

Full description

Bibliographic Details
Main Authors: Rota, Christopher M, Brown, Alexander T, Addleson, Emily, Ives, Clara, Trumper, Ella, Pelton, Kristine, Teh, Wei Pin, Schniederjan, Matthew J, Castellino, Robert Craig, Buhrlage, Sara, Lauffenburger, Douglas A, Ligon, Keith L, Griffith, Linda G, Segal, Rosalind A
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:English
Published: Oxford University Press (OUP) 2023
Online Access:https://hdl.handle.net/1721.1/147854
_version_ 1826210420014186496
author Rota, Christopher M
Brown, Alexander T
Addleson, Emily
Ives, Clara
Trumper, Ella
Pelton, Kristine
Teh, Wei Pin
Schniederjan, Matthew J
Castellino, Robert Craig
Buhrlage, Sara
Lauffenburger, Douglas A
Ligon, Keith L
Griffith, Linda G
Segal, Rosalind A
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Rota, Christopher M
Brown, Alexander T
Addleson, Emily
Ives, Clara
Trumper, Ella
Pelton, Kristine
Teh, Wei Pin
Schniederjan, Matthew J
Castellino, Robert Craig
Buhrlage, Sara
Lauffenburger, Douglas A
Ligon, Keith L
Griffith, Linda G
Segal, Rosalind A
author_sort Rota, Christopher M
collection MIT
description Abstract Background. Pediatric gliomas comprise a diverse set of brain tumor entities that have substantial long-term ramifications for patient survival and quality of life. However, the study of these tumors is currently limited due to a lack of authentic models. Additionally, many aspects of pediatric brain tumor biology, such as tumor cell invasiveness, have been difficult to study with currently available tools. To address these issues, we developed a synthetic extracellular matrix (sECM)-based culture system to grow and study primary pediatric brain tumor cells. Methods. We developed a brain-like sECM material as a supportive scaffold for the culture of primary, patientderived pediatric glioma cells and established patient-derived cell lines. Primary juvenile brainstem-derived murine astrocytes were used as a feeder layer to support the growth of primary human tumor cells. Results. We found that our culture system facilitated the proliferation of various primary pediatric brain tumors, including low-grade gliomas, and enabled ex vivo testing of investigational therapeutics. Additionally, we found that tuning this sECM material allowed us to assess high-grade pediatric glioma cell invasion and evaluate therapeutic interventions targeting invasive behavior. Conclusion. Our sECM culture platform provides a multipurpose tool for pediatric brain tumor researchers that enables both a wide breadth of biological assays and the cultivation of diverse tumor types.
first_indexed 2024-09-23T14:49:12Z
format Article
id mit-1721.1/147854
institution Massachusetts Institute of Technology
language English
last_indexed 2024-09-23T14:49:12Z
publishDate 2023
publisher Oxford University Press (OUP)
record_format dspace
spelling mit-1721.1/1478542023-02-04T03:12:13Z Synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas Rota, Christopher M Brown, Alexander T Addleson, Emily Ives, Clara Trumper, Ella Pelton, Kristine Teh, Wei Pin Schniederjan, Matthew J Castellino, Robert Craig Buhrlage, Sara Lauffenburger, Douglas A Ligon, Keith L Griffith, Linda G Segal, Rosalind A Massachusetts Institute of Technology. Department of Biological Engineering Abstract Background. Pediatric gliomas comprise a diverse set of brain tumor entities that have substantial long-term ramifications for patient survival and quality of life. However, the study of these tumors is currently limited due to a lack of authentic models. Additionally, many aspects of pediatric brain tumor biology, such as tumor cell invasiveness, have been difficult to study with currently available tools. To address these issues, we developed a synthetic extracellular matrix (sECM)-based culture system to grow and study primary pediatric brain tumor cells. Methods. We developed a brain-like sECM material as a supportive scaffold for the culture of primary, patientderived pediatric glioma cells and established patient-derived cell lines. Primary juvenile brainstem-derived murine astrocytes were used as a feeder layer to support the growth of primary human tumor cells. Results. We found that our culture system facilitated the proliferation of various primary pediatric brain tumors, including low-grade gliomas, and enabled ex vivo testing of investigational therapeutics. Additionally, we found that tuning this sECM material allowed us to assess high-grade pediatric glioma cell invasion and evaluate therapeutic interventions targeting invasive behavior. Conclusion. Our sECM culture platform provides a multipurpose tool for pediatric brain tumor researchers that enables both a wide breadth of biological assays and the cultivation of diverse tumor types. 2023-02-03T15:56:30Z 2023-02-03T15:56:30Z 2022 2023-02-03T15:44:48Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147854 Rota, Christopher M, Brown, Alexander T, Addleson, Emily, Ives, Clara, Trumper, Ella et al. 2022. "Synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas." Neuro-Oncology Advances, 4 (1). en 10.1093/NOAJNL/VDAC049 Neuro-Oncology Advances Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Oxford University Press (OUP) Oxford University Press
spellingShingle Rota, Christopher M
Brown, Alexander T
Addleson, Emily
Ives, Clara
Trumper, Ella
Pelton, Kristine
Teh, Wei Pin
Schniederjan, Matthew J
Castellino, Robert Craig
Buhrlage, Sara
Lauffenburger, Douglas A
Ligon, Keith L
Griffith, Linda G
Segal, Rosalind A
Synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas
title Synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas
title_full Synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas
title_fullStr Synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas
title_full_unstemmed Synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas
title_short Synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas
title_sort synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas
url https://hdl.handle.net/1721.1/147854
work_keys_str_mv AT rotachristopherm syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT brownalexandert syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT addlesonemily syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT ivesclara syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT trumperella syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT peltonkristine syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT tehweipin syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT schniederjanmatthewj syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT castellinorobertcraig syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT buhrlagesara syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT lauffenburgerdouglasa syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT ligonkeithl syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT griffithlindag syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas
AT segalrosalinda syntheticextracellularmatricesandastrocytesprovideasupportivemicroenvironmentforthecultivationandinvestigationofprimarypediatricgliomas