Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, the Netherlands.
Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, the Netherlands; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands.
Cell Stem Cell. 2021 Aug 5;28(8):1380-1396.e6. doi: 10.1016/j.stem.2021.03.012. Epub 2021 Apr 13.
Cervical cancer is a common gynecological malignancy often caused by high-risk human papillomavirus. There is a paucity of human-derived culture systems to study the cervical epithelium and the cancers derived thereof. Here we describe a long-term culturing protocol for ecto- and endocervical epithelia that generates 3D organoids that stably recapitulate the two tissues of origin. As evidenced for HSV-1, organoid-based cervical models may serve to study sexually transmitted infections. Starting from Pap brush material, a small biobank of tumoroids derived from affected individuals was established that retained the causative human papillomavirus (HPV) genomes. One of these uniquely carried the poorly characterized HPV30 subtype, implying a potential role in carcinogenesis. The tumoroids displayed differential responses to common chemotherapeutic agents and grew as xenografts in mice. This study describes an experimental platform for cervical (cancer) research and for future personalized medicine approaches.
宫颈癌是一种常见的妇科恶性肿瘤，通常由高危型人乳头瘤病毒引起。目前用于研究宫颈上皮及其衍生癌症的人类来源培养系统还很少。在这里，我们描述了一种用于研究宫颈外和宫颈内上皮的长期培养方案，该方案可生成稳定重现两种原始组织的 3D 类器官。正如单纯疱疹病毒 1 所证明的那样，基于类器官的宫颈模型可用于研究性传播感染。从巴氏刷材料开始，建立了一个由受影响个体衍生的肿瘤类器官的小型生物库，这些肿瘤类器官保留了致病的人乳头瘤病毒 (HPV) 基因组。其中一个独特地携带了尚未充分表征的 HPV30 亚型，这意味着其可能在致癌作用中发挥作用。肿瘤类器官对常见化疗药物表现出不同的反应，并在小鼠中作为异种移植物生长。本研究描述了用于宫颈（癌）研究和未来个性化医学方法的实验平台。
