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• Rapid and efficient generation of uniformly-sized organoids from single cell suspensions
• Consistent gene expression in two high-fidelity ovarian cancer organoid models
• Uniformly-sized ovarian cancer organoids show consistent, reliable drug responses for personalized chemotherapy resistance tests
Ovarian cancer, a common gynecologic tumor, is associated with a high mortality, due to challenges in early detection within the reproductive system. According to our previous research, cultivating patient-specific organoids from mechanically sheared tissues can be utilized for drug response evaluation but has limitations for high-throughput screening efficiency due to their inconsistent size. In this research, we focused on organoids developed from single-cell suspensions to address the critical requirement for uniformity in organoid size. By the day 3 of culture, single-cell suspensions rapidly and spontaneously aggregated into spherical structures with a more consistent size. Notably, the organoids of sample OVA-37 were ten times larger after 8 days of culture. Transcriptomic analysis was used to compare the two organoid culture techniques, demonstrating that the variations between different organoid culture methods were minimal, with higher variability observed among patients. Gene set enrichment analysis (GSEA) revealed only minor discrepancies in specific pathways, such as TGF-β and tight junctions. Furthermore, treatment with carboplatin in a 96-well plate setup resulted in reproducible drug responses, as evidenced by coefficients of variation lower than 40%. This finding suggests that single-cell suspension-cultured organoids can be employed for reproducible high-throughput drug screening. This approach holds potential for personalized drug screening in ovarian cancer and may contribute to the development of novel therapeutic strategies.
Forstner, R. Early detection of ovarian cancer. European Radiology, 2020, 30(10): 5370–5373. https://doi.org/10.1007/s00330-020-06937-z
Xie, W. W., Sun, H. Z., Li, X. D., Lin, F. K., Wang, Z. L., Wang, X. P. Ovarian cancer: Epigenetics, drug resistance, and progression. Cancer Cell International, 2021, 21(1): 434. https://doi.org/10.1186/s12935-021-02136-y
Konstantinopoulos, P. A., Matulonis, U. A. Clinical and translational advances in ovarian cancer therapy. Nature Cancer, 2023, 4(9): 1239–1257. https://doi.org/10.1038/s43018-023-00617-9
Matsui, T., Shinozawa, T. Human organoids for predictive toxicology research and drug development. Frontiers in Genetics, 2021, 12: 767621. https://doi.org/10.3389/fgene.2021.767621
Granat, L. M., Kambhampati, O., Klosek, S., Niedzwecki, B., Parsa, K., Zhang, D. The promises and challenges of patient-derived tumor organoids in drug development and precision oncology. Animal Models and Experimental Medicine, 2019, 2(3): 150–161. https://doi.org/10.1002/ame2.12077
Kondo, J., Inoue, M. Application of cancer organoid model for drug screening and personalized therapy. Cells, 2019, 8(5): 470. https://doi.org/10.3390/cells8050470
Jung, Y. H., Park, K., Kim, M., Oh, H., Choi, D. H., Ahn, J., Lee, S. B., Na, K., Min, B. S., Kim, J. A. et al. Development of an extracellular matrix plate for drug screening using patient-derived tumor organoids. BioChip Journal, 2023, 17(2): 284–292. https://doi.org/10.1007/s13206-023-00099-y
Mahbubi, R., Yousefi, N., Hamidieh, A., Gholizadeh, F., Sisakht, M. M. Tumor organoid as a drug screening platform for cancer research. Current Stem Cell Research & Therapy, 2023, 19(9): 1210–1250. https://doi.org/10.2174/011574888X268366230922080423
Spiller, E. R., Ung, N., Kim, S., Patsch, K., Lau, R., Strelez, C., Doshi, C., Choung, S., Choi, B., Juarez Rosales, E. F. et al. Imaging-based machine learning analysis of patient-derived tumor organoid drug response. Frontiers in Oncology, 2021, 11: 771173. https://doi.org/10.3389/fonc.2021.771173
Zhou, Z. L., Cong, L. L., Cong, X. L. Patient-derived organoids in precision medicine: Drug screening, organoid-on-a-chip and living organoid biobank. Frontiers in Oncology, 2021, 11: 762184. https://doi.org/10.3389/fonc.2021.762184
Wijler, L., Mateos, J. G., Nguyen, M., Staes, A. A. L., van Seters, L., Hasan, L. A., Tiroille, V., Herpers, B., Price, L., Madej, M. et al. Abstract 198: Pan-cancer assay-ready organoid drug screening with robust, reproducible and clinically-relevant output. Cancer Research, 2023, 83(7_Supplement): 198. https://doi.org/10.1158/1538-7445.AM2023-198
Yan, Y. T., Liu, J. L., Lawrence, A., Dykstra, M. J., Fannin, R., Gerrish, K., Tucker, C. J., Scappini, E., Dixon, D. Prolonged cadmium exposure alters benign uterine fibroid cell behavior, extracellular matrix components, and TGFB signaling. The FASEB Journal, 2021, 35(8): e21738. https://doi.org/10.1096/fj.202100354r
Pickup, M. W., Owens, P., Moses, H. L. TGF-β, bone morphogenetic protein, and activin signaling and the tumor microenvironment. Cold Spring Harbor Perspectives in Biology, 2017, 9(5): a022285. https://doi.org/10.1101/cshperspect.a022285
Nehme, Z., Roehlen, N., Dhawan, P., Baumert, T. F. Tight junction protein signaling and cancer biology. Cells, 2023, 12(2): 243. https://doi.org/10.3390/cells12020243
Food Science of Animal Products published by Tsinghua University Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
