A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment
Abstract Glioblastoma is an aggressive brain cancer characterized by diffuse infiltration. Infiltrated glioma cells persist in the brain post-resection where they interact with glial cells and experience interstitial fluid flow. We use patient-derived glioma stem cells and human glial cells (i.e., a...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-022-00290-8 |
| _version_ | 1797642216258142208 |
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| author | R. C. Cornelison J. X. Yuan K. M. Tate A. Petrosky G. F. Beeghly M. Bloomfield S. C. Schwager A. L. Berr C. A. Stine D. Cimini F. F. Bafakih J. W. Mandell B. W. Purow B. J. Horton J. M. Munson |
| author_facet | R. C. Cornelison J. X. Yuan K. M. Tate A. Petrosky G. F. Beeghly M. Bloomfield S. C. Schwager A. L. Berr C. A. Stine D. Cimini F. F. Bafakih J. W. Mandell B. W. Purow B. J. Horton J. M. Munson |
| author_sort | R. C. Cornelison |
| collection | DOAJ |
| description | Abstract Glioblastoma is an aggressive brain cancer characterized by diffuse infiltration. Infiltrated glioma cells persist in the brain post-resection where they interact with glial cells and experience interstitial fluid flow. We use patient-derived glioma stem cells and human glial cells (i.e., astrocytes and microglia) to create a four-component 3D model of this environment informed by resected patient tumors. We examine metrics for invasion, proliferation, and putative stemness in the context of glial cells, fluid forces, and chemotherapies. While the responses are heterogeneous across seven patient-derived lines, interstitial flow significantly increases glioma cell proliferation and stemness while glial cells affect invasion and stemness, potentially related to CCL2 expression and differential activation. In a screen of six drugs, we find in vitro expression of putative stemness marker CD71, but not viability at drug IC50, to predict murine xenograft survival. We posit this patient-informed, infiltrative tumor model as a novel advance toward precision medicine in glioblastoma treatment. |
| first_indexed | 2024-03-11T13:57:00Z |
| format | Article |
| id | doaj.art-42c40b9824ab4d4892cb00cdede09d50 |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-11T13:57:00Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-42c40b9824ab4d4892cb00cdede09d502023-11-02T06:14:46ZengNature Portfolionpj Precision Oncology2397-768X2022-07-016111410.1038/s41698-022-00290-8A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironmentR. C. Cornelison0J. X. Yuan1K. M. Tate2A. Petrosky3G. F. Beeghly4M. Bloomfield5S. C. Schwager6A. L. Berr7C. A. Stine8D. Cimini9F. F. Bafakih10J. W. Mandell11B. W. Purow12B. J. Horton13J. M. Munson14Department of Biomedical Engineering, University of Massachusetts AmherstDepartment of Biomedical Engineering, University of VirginiaDepartment of Biomedical Engineering & Mechanics, Virginia TechDepartment of Biomedical Engineering & Mechanics, Virginia TechDepartment of Biomedical Engineering, University of VirginiaDepartment of Biological Sciences and Fralin Life Sciences Institute, Virginia TechDepartment of Biomedical Engineering, University of VirginiaDepartment of Biomedical Engineering, University of VirginiaDepartment of Biomedical Engineering & Mechanics, Virginia TechDepartment of Biological Sciences and Fralin Life Sciences Institute, Virginia TechUniversity of Virginia School of MedicineUniversity of Virginia School of MedicineUniversity of Virginia School of MedicineUniversity of Virginia School of MedicineDepartment of Biomedical Engineering & Mechanics, Virginia TechAbstract Glioblastoma is an aggressive brain cancer characterized by diffuse infiltration. Infiltrated glioma cells persist in the brain post-resection where they interact with glial cells and experience interstitial fluid flow. We use patient-derived glioma stem cells and human glial cells (i.e., astrocytes and microglia) to create a four-component 3D model of this environment informed by resected patient tumors. We examine metrics for invasion, proliferation, and putative stemness in the context of glial cells, fluid forces, and chemotherapies. While the responses are heterogeneous across seven patient-derived lines, interstitial flow significantly increases glioma cell proliferation and stemness while glial cells affect invasion and stemness, potentially related to CCL2 expression and differential activation. In a screen of six drugs, we find in vitro expression of putative stemness marker CD71, but not viability at drug IC50, to predict murine xenograft survival. We posit this patient-informed, infiltrative tumor model as a novel advance toward precision medicine in glioblastoma treatment.https://doi.org/10.1038/s41698-022-00290-8 |
| spellingShingle | R. C. Cornelison J. X. Yuan K. M. Tate A. Petrosky G. F. Beeghly M. Bloomfield S. C. Schwager A. L. Berr C. A. Stine D. Cimini F. F. Bafakih J. W. Mandell B. W. Purow B. J. Horton J. M. Munson A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment npj Precision Oncology |
| title | A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment |
| title_full | A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment |
| title_fullStr | A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment |
| title_full_unstemmed | A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment |
| title_short | A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment |
| title_sort | patient designed tissue engineered model of the infiltrative glioblastoma microenvironment |
| url | https://doi.org/10.1038/s41698-022-00290-8 |
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