A Promising New Model: Establishment of Patient‐Derived Organoid Models Covering HPV‐Related Cervical Pre‐Cancerous Lesions and Their Cancers
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Published:2024-01-16
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ISSN:2198-3844
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Container-title:Advanced Science
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language:en
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Short-container-title:Advanced Science
Author:
Hu Bai12,
Wang Renjie12,
Wu Di12,
Long Rui12,
Fan Junpeng12,
Hu Zhe12,
Hu Xingyuan12,
Ma Ding12,
Li Fang3,
Sun Chaoyang12,
Liao Shujie12ORCID
Affiliation:
1. Department of Gynecology and Obstetrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 China
2. National Clinical Research Center for Obstetrics and Gynecology Cancer Biology Research Center (Key Laboratory of the Ministry of Education) Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 China
3. Department of Obstetrics and Gynecology Shanghai East Hospital School of Medicine Tongji University Shanghai 200120 China
Abstract
AbstractThe lack of human‐derived in vitro models that recapitulate cervical pre‐cancerous lesions has been the bottleneck in researching human papillomavirus (HPV) infection‐associated pre‐cancerous lesions and cancers for a long time. Here, a long‐term 3D organoid culture protocol for high‐grade squamous intraepithelial lesions and cervical squamous cell carcinoma that stably recapitulates the two tissues of origin is described. Originating from human‐derived samples, a small biobank of cervical pre‐tumoroids and tumoroids that faithfully retains genomic and transcriptomic characteristics as well as the causative HPV genome is established. Cervical pre‐tumoroids and tumoroids show differential responses to common chemotherapeutic agents and grow differently as xenografts in mice. By coculture organoid models with peripheral blood immune cells (PBMCs) stimulated by HPV antigenic peptides, it is illustrated that both organoid models respond differently to immunized PBMCs, supporting organoids as reliable and powerful tools for studying virus‐specific T‐cell responses and screening therapeutic HPV vaccines. In this study, a model of cervical pre‐cancerous lesions containing HPV is established for the first time, overcoming the bottleneck of the current model of human cervical pre‐cancerous lesions. This study establishes an experimental platform and biobanks for in vitro mechanistic research, therapeutic vaccine screening, and personalized treatment for HPV‐related cervical diseases.
Funder
National Natural Science Foundation of China
National Key Research and Development Program of China
Natural Science Foundation of Hubei Province
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)