AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
PDF (5.7 MB)
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Article | Open Access | Online First

Crossroad of ovarian cancer organoid culture: Single cell suspension and mechanically sheared fragment

Lanyang Li1,§Jiping Liu1,§Qi Cao2,§Yuqing Zhao2Yanghua Shi1Chen Wang1Jian Zhang1Mingjie Rong1Xiang Tao2Wei Deng3,4( )Chunhui Cai1( )Xinxin Han1,5( )
Shanghai Lisheng Biotech, Shanghai 200092, China
Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Department of Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China
Organ Regeneration X Lab, LiSheng East China Institute of Biotechnology, Peking University, Nantong 226299, China

§ Lanyang Li, Jiping Liu, and Qi Cao contributed equally to this work.

Show Author Information

Highlights

• 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

Graphical Abstract

This study explores the cultivation of uniformly-sized ovarian cancer organoids from single-cell suspensions, addressing challenges in high-throughput drug screening and providing insights into personalized treatment strategies against chemotherapy resistance.

Abstract

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.

References

[1]

Forstner, R. Early detection of ovarian cancer. European Radiology, 2020, 30(10): 5370–5373. https://doi.org/10.1007/s00330-020-06937-z

[2]

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

[3]

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

[4]

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

[5]

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

[6]
Cao, Q., Li, L. Y., Zhao, Y. Q., Wang, C., Shi, Y. H., Tao, X., Cai, C. H., Han, X. X. PARPi decreased primary ovarian cancer organoid growth through early apoptosis and base excision repair pathway. Cell Transplantation, 2023 , 32. https://doi.org/10.1177/09636897231187996
[7]

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

[8]

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

[9]

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

[10]

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

[11]

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

[12]

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

[13]

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

[14]

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

[15]

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

Cell Organoid
Cite this article:
Li L, Liu J, Cao Q, et al. Crossroad of ovarian cancer organoid culture: Single cell suspension and mechanically sheared fragment. Cell Organoid, 2024, https://doi.org/10.26599/CO.2024.9410005

664

Views

168

Downloads

1

Crossref

Altmetrics

Received: 06 February 2024
Revised: 26 March 2024
Accepted: 12 May 2024
Published: 30 July 2024
© The Author(s) 2024. Published by Tsinghua University Press

The articles published in this open access journal are distributed under the termsof the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution andreproduction in any medium, provided the original work is properly cited.

Return