Impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity.

Autor: DeStefanis RA; Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, 6507 WIMR2, Madison, WI, 53705, USA., Kratz JD; Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, 6507 WIMR2, Madison, WI, 53705, USA.; University of Wisconsin Carbone Cancer Center, Madison, WI, USA., Olson AM; Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, 6507 WIMR2, Madison, WI, 53705, USA., Sunil A; Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, 6507 WIMR2, Madison, WI, 53705, USA., DeZeeuw AK; Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, 6507 WIMR2, Madison, WI, 53705, USA., Gillette AA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA., Sha GC; Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, 6507 WIMR2, Madison, WI, 53705, USA., Johnson KA; Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, 6507 WIMR2, Madison, WI, 53705, USA., Pasch CA; University of Wisconsin Carbone Cancer Center, Madison, WI, USA., Clipson L; McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, WI, USA., Skala MC; University of Wisconsin Carbone Cancer Center, Madison, WI, USA.; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.; Morgridge Institute for Research, Madison, WI, USA., Deming DA; Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, 6507 WIMR2, Madison, WI, 53705, USA. ddeming@medicine.wisc.edu.; University of Wisconsin Carbone Cancer Center, Madison, WI, USA. ddeming@medicine.wisc.edu.; McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, WI, USA. ddeming@medicine.wisc.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Mar 25; Vol. 12 (1), pp. 5205. Date of Electronic Publication: 2022 Mar 25.
DOI: 10.1038/s41598-022-08937-z
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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