Multi-Cell Type Glioblastoma Tumor Spheroids for Evaluating Sub-Population-Specific Drug Response
Glioblastoma (GBM) is a lethal, incurable form of cancer in the brain. Even with maximally aggressive surgery and chemoradiotherapy, median patient survival is 14.5 months. These tumors infiltrate normal brain tissue, are surgically incurable, and universally recur. GBMs are characterized by genetic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2020.538663/full |
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| author | Hemamylammal Sivakumar Hemamylammal Sivakumar Hemamylammal Sivakumar Mahesh Devarasetty David E. Kram David E. Kram Roy E. Strowd Roy E. Strowd Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal |
| author_facet | Hemamylammal Sivakumar Hemamylammal Sivakumar Hemamylammal Sivakumar Mahesh Devarasetty David E. Kram David E. Kram Roy E. Strowd Roy E. Strowd Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal |
| author_sort | Hemamylammal Sivakumar |
| collection | DOAJ |
| description | Glioblastoma (GBM) is a lethal, incurable form of cancer in the brain. Even with maximally aggressive surgery and chemoradiotherapy, median patient survival is 14.5 months. These tumors infiltrate normal brain tissue, are surgically incurable, and universally recur. GBMs are characterized by genetic, epigenetic, and microenvironmental heterogeneity, and they evolve spontaneously over time and as a result of treatment. However, tracking such heterogeneity in real time in response to drug treatments has been impossible. Here we describe the development of an in vitro GBM tumor organoid model that is comprised of five distinct cellular subpopulations (4 GBM cell lines that represent GBM subpopulations and 1 astrocyte line), each fluorescently labeled with a different color. These multi-cell type GBM organoids are then embedded in a brain-like hyaluronic acid hydrogel for subsequent studies involving drug treatments and tracking of changes in relative numbers of each fluorescently unique subpopulation. This approach allows for the visual assessment of drug influence on individual subpopulations within GBM, and in future work can be expanded to supporting studies using patient tumor biospecimen-derived cells for personalized diagnostics. |
| first_indexed | 2024-12-13T12:41:05Z |
| format | Article |
| id | doaj.art-170771331f584c128c2d9fe08c333cc4 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-13T12:41:05Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-170771331f584c128c2d9fe08c333cc42022-12-21T23:45:38ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-09-01810.3389/fbioe.2020.538663538663Multi-Cell Type Glioblastoma Tumor Spheroids for Evaluating Sub-Population-Specific Drug ResponseHemamylammal Sivakumar0Hemamylammal Sivakumar1Hemamylammal Sivakumar2Mahesh Devarasetty3David E. Kram4David E. Kram5Roy E. Strowd6Roy E. Strowd7Aleksander Skardal8Aleksander Skardal9Aleksander Skardal10Aleksander Skardal11Aleksander Skardal12Aleksander Skardal13Aleksander Skardal14Department of Biomedical Engineering, The Ohio State University, Columbus, OH, United StatesThe Ohio State University and Arthur G. James Comprehensive Cancer Center, Columbus, OH, United StatesWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesSection of Pediatric Hematology and Oncology, Department of Pediatrics, Wake Forest Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC, United StatesComprehensive Cancer Center at Wake Forest Baptist Medical, Winston-Salem, NC, United StatesComprehensive Cancer Center at Wake Forest Baptist Medical, Winston-Salem, NC, United StatesDepartment of Neurology, Wake Forest Baptist Medical Center, Winston-Salem, NC, United StatesDepartment of Biomedical Engineering, The Ohio State University, Columbus, OH, United StatesThe Ohio State University and Arthur G. James Comprehensive Cancer Center, Columbus, OH, United StatesWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesComprehensive Cancer Center at Wake Forest Baptist Medical, Winston-Salem, NC, United StatesVirginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Molecular Medicine and Translational Science, Wake Forest School of Medicine, Winston-Salem, NC, United StatesGlioblastoma (GBM) is a lethal, incurable form of cancer in the brain. Even with maximally aggressive surgery and chemoradiotherapy, median patient survival is 14.5 months. These tumors infiltrate normal brain tissue, are surgically incurable, and universally recur. GBMs are characterized by genetic, epigenetic, and microenvironmental heterogeneity, and they evolve spontaneously over time and as a result of treatment. However, tracking such heterogeneity in real time in response to drug treatments has been impossible. Here we describe the development of an in vitro GBM tumor organoid model that is comprised of five distinct cellular subpopulations (4 GBM cell lines that represent GBM subpopulations and 1 astrocyte line), each fluorescently labeled with a different color. These multi-cell type GBM organoids are then embedded in a brain-like hyaluronic acid hydrogel for subsequent studies involving drug treatments and tracking of changes in relative numbers of each fluorescently unique subpopulation. This approach allows for the visual assessment of drug influence on individual subpopulations within GBM, and in future work can be expanded to supporting studies using patient tumor biospecimen-derived cells for personalized diagnostics.https://www.frontiersin.org/article/10.3389/fbioe.2020.538663/fullglioblastomaspheroidorganoiddrug responsetumor heterogeneity |
| spellingShingle | Hemamylammal Sivakumar Hemamylammal Sivakumar Hemamylammal Sivakumar Mahesh Devarasetty David E. Kram David E. Kram Roy E. Strowd Roy E. Strowd Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal Aleksander Skardal Multi-Cell Type Glioblastoma Tumor Spheroids for Evaluating Sub-Population-Specific Drug Response Frontiers in Bioengineering and Biotechnology glioblastoma spheroid organoid drug response tumor heterogeneity |
| title | Multi-Cell Type Glioblastoma Tumor Spheroids for Evaluating Sub-Population-Specific Drug Response |
| title_full | Multi-Cell Type Glioblastoma Tumor Spheroids for Evaluating Sub-Population-Specific Drug Response |
| title_fullStr | Multi-Cell Type Glioblastoma Tumor Spheroids for Evaluating Sub-Population-Specific Drug Response |
| title_full_unstemmed | Multi-Cell Type Glioblastoma Tumor Spheroids for Evaluating Sub-Population-Specific Drug Response |
| title_short | Multi-Cell Type Glioblastoma Tumor Spheroids for Evaluating Sub-Population-Specific Drug Response |
| title_sort | multi cell type glioblastoma tumor spheroids for evaluating sub population specific drug response |
| topic | glioblastoma spheroid organoid drug response tumor heterogeneity |
| url | https://www.frontiersin.org/article/10.3389/fbioe.2020.538663/full |
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