A Promising New Model : Establishment of Patient-Derived Organoid Models Covering HPV-Related Cervical Pre-Cancerous Lesions and Their Cancers

© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH..

The 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 11(2024), 12 vom: 01. März, Seite e2302340

Sprache:

Englisch

Beteiligte Personen:

Hu, Bai [VerfasserIn]
Wang, Renjie [VerfasserIn]
Wu, Di [VerfasserIn]
Long, Rui [VerfasserIn]
Fan, Junpeng [VerfasserIn]
Hu, Zhe [VerfasserIn]
Hu, Xingyuan [VerfasserIn]
Ma, Ding [VerfasserIn]
Li, Fang [VerfasserIn]
Sun, Chaoyang [VerfasserIn]
Liao, Shujie [VerfasserIn]

Links:

Volltext

Themen:

Cervical cancer
Coculture
Human papillomavirus
Journal Article
Organoids
Squamous intraepithelial lesion

Anmerkungen:

Date Completed 28.03.2024

Date Revised 29.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1002/advs.202302340

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM367197200