Impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity
Abstract Representative models are needed to screen new therapies for patients with cancer. Cancer organoids are a leap forward as a culture model that faithfully represents the disease. Mouse-derived cancer organoids (MDCOs) are becoming increasingly popular, however there has yet to be a standardi...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-03-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-08937-z |
| _version_ | 1818353594361970688 |
|---|---|
| author | Rebecca A. DeStefanis Jeremy D. Kratz Autumn M. Olson Aishwarya Sunil Alyssa K. DeZeeuw Amani A. Gillette Gioia C. Sha Katherine A. Johnson Cheri A. Pasch Linda Clipson Melissa C. Skala Dustin A. Deming |
| author_facet | Rebecca A. DeStefanis Jeremy D. Kratz Autumn M. Olson Aishwarya Sunil Alyssa K. DeZeeuw Amani A. Gillette Gioia C. Sha Katherine A. Johnson Cheri A. Pasch Linda Clipson Melissa C. Skala Dustin A. Deming |
| author_sort | Rebecca A. DeStefanis |
| collection | DOAJ |
| description | Abstract Representative models are needed to screen new therapies for patients with cancer. Cancer organoids are a leap forward as a culture model that faithfully represents the disease. Mouse-derived cancer organoids (MDCOs) are becoming increasingly popular, however there has yet to be a standardized method to assess therapeutic response and identify subpopulation heterogeneity. There are multiple factors unique to organoid culture that could affect how therapeutic response and MDCO heterogeneity are assessed. Here we describe an analysis of nearly 3500 individual MDCOs where individual organoid morphologic tracking was performed. Change in MDCO diameter was assessed in the presence of control media or targeted therapies. Individual organoid tracking was identified to be more sensitive to treatment response than well-level assessment. The impact of different generations of mice of the same genotype, different regions of the colon, and organoid specific characteristics including baseline size, passage number, plating density, and location within the matrix were examined. Only the starting size of the MDCO altered the subsequent growth. These results were corroborated using ~ 1700 patient-derived cancer organoids (PDCOs) isolated from 19 patients. Here we establish organoid culture parameters for individual organoid morphologic tracking to determine therapeutic response and growth/response heterogeneity for translational studies. |
| first_indexed | 2024-12-13T19:12:01Z |
| format | Article |
| id | doaj.art-0850400bc08146908046414b05f6fcca |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T19:12:01Z |
| publishDate | 2022-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0850400bc08146908046414b05f6fcca2022-12-21T23:34:22ZengNature PortfolioScientific Reports2045-23222022-03-0112111410.1038/s41598-022-08937-zImpact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneityRebecca A. DeStefanis0Jeremy D. Kratz1Autumn M. Olson2Aishwarya Sunil3Alyssa K. DeZeeuw4Amani A. Gillette5Gioia C. Sha6Katherine A. Johnson7Cheri A. Pasch8Linda Clipson9Melissa C. Skala10Dustin A. Deming11Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-MadisonDivision of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-MadisonDivision of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-MadisonDivision of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-MadisonDivision of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-MadisonDepartment of Biomedical Engineering, University of Wisconsin-MadisonDivision of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-MadisonDivision of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-MadisonUniversity of Wisconsin Carbone Cancer CenterMcArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-MadisonUniversity of Wisconsin Carbone Cancer CenterDivision of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-MadisonAbstract Representative models are needed to screen new therapies for patients with cancer. Cancer organoids are a leap forward as a culture model that faithfully represents the disease. Mouse-derived cancer organoids (MDCOs) are becoming increasingly popular, however there has yet to be a standardized method to assess therapeutic response and identify subpopulation heterogeneity. There are multiple factors unique to organoid culture that could affect how therapeutic response and MDCO heterogeneity are assessed. Here we describe an analysis of nearly 3500 individual MDCOs where individual organoid morphologic tracking was performed. Change in MDCO diameter was assessed in the presence of control media or targeted therapies. Individual organoid tracking was identified to be more sensitive to treatment response than well-level assessment. The impact of different generations of mice of the same genotype, different regions of the colon, and organoid specific characteristics including baseline size, passage number, plating density, and location within the matrix were examined. Only the starting size of the MDCO altered the subsequent growth. These results were corroborated using ~ 1700 patient-derived cancer organoids (PDCOs) isolated from 19 patients. Here we establish organoid culture parameters for individual organoid morphologic tracking to determine therapeutic response and growth/response heterogeneity for translational studies.https://doi.org/10.1038/s41598-022-08937-z |
| spellingShingle | Rebecca A. DeStefanis Jeremy D. Kratz Autumn M. Olson Aishwarya Sunil Alyssa K. DeZeeuw Amani A. Gillette Gioia C. Sha Katherine A. Johnson Cheri A. Pasch Linda Clipson Melissa C. Skala Dustin A. Deming Impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity Scientific Reports |
| title | Impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity |
| title_full | Impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity |
| title_fullStr | Impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity |
| title_full_unstemmed | Impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity |
| title_short | Impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity |
| title_sort | impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity |
| url | https://doi.org/10.1038/s41598-022-08937-z |
| work_keys_str_mv | AT rebeccaadestefanis impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity AT jeremydkratz impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity AT autumnmolson impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity AT aishwaryasunil impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity AT alyssakdezeeuw impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity AT amaniagillette impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity AT gioiacsha impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity AT katherineajohnson impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity AT cheriapasch impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity AT lindaclipson impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity AT melissacskala impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity AT dustinademing impactofbaselinecultureconditionsofcancerorganoidswhendeterminingtherapeuticresponseandtumorheterogeneity |