Efficient Use of Patient-Derived Organoids as a Preclinical Model for Gynecologic Tumors
Abstract
Objective The relevance of patient-derived cancer cells has been recently increasing, particularly in terms of drug discovery and precision medicine. Whereas Matrigel-based organoid culture is a promising technique that enables infinite proliferation of cells from many types of organs in a physiological condition, its validity in gynecologic tumors remains to be established. To address this issue, we aimed at developing an efficient method for organoid culture of both ovarian and endometrial tumors.Methods We conducted 3D culture of 21 gynecologic tumors following our original and modified protocol for Matrigel bilayer organoid culture. We investigated whether propagated organoids retained various features of the original tumors by histopathological examination and targeted genome sequencing.Results We customized the protocol we previously optimized for murine normal and cancer tissues, so as to circumvent the digestion-resistant nature inherent to gynecologic tumors. Indeed, this modified protocol improved the success rate from 45 to 90%, for robust propagation of organoids from tumors with various stages and subtypes. Finally, 14 patient-derived organoids were established. The recovered organoids were enriched for cancer cells that retained many aspects of the original tumors, including histological features, mutation profiles, and intra-tumoral heterogeneity. A subset of the expanded organoids could develop xenografts in immunodeficient mice, potentially paving the way to drug screening in vivo. Drug response assay in vitro for paclitaxel and cisplatin was feasible using organoid-derived spheroids.Conclusions We showed that patient-derived organoids closely resembled the original gynecologic tumors, and thereby would serve as a promising resource for preclinical studies.
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When grown in a modified Matrigel bilayer, organoids from MOCs could reproduce behaviors of their derivative cancer, such as production of mucin and a cystic morphology.
“When grown in a modified Matrigel bilayer, organoids from MOCs could reproduce behaviors of their derivative cancer, such as production of mucin and a cystic morphology (Maru et al., 2019).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Maru et al., 2019
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- Authors
- Maru, Y., Tanaka, N., Itami, M., & Hippo, Y.
- Affiliations
- Chiba Cancer Center Research Institute (JP)
- Chiba Cancer Center (JP)
- Corresponding author
- Hippo, Yoshitaka
- Venue
- Gynecologic Oncology
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 154
- Issue
- 1
- Pages
- 189-198
- ISSN
- 0090-8258 (ISSN-L)
- OpenAlex
- W2946001968
- Cited by
- 162
- References
- 39
- Citations by year
- 2026: 12 · 2025: 23 · 2024: 28 · 2023: 21 · 2022: 25 · 2021: 31 · 2020: 17 · 2019: 5
- FWCI
- 8.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gynecologic Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- patient-derived organoids, gynecologic cancer, ovarian cancer, endometrial cancer, tumor heterogeneity, paclitaxel, cisplatin, drug screening, 3D cell culture
- MeSH terms
- Animals, Drug Screening Assays, Antitumor, Female, Humans, Mice, Inbred BALB C, Mice, Nude, Neoplasm Staging, Organoids, Ovarian Neoplasms, Endometrial Neoplasms, Tissue Culture Techniques, Mice
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