Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, China.
Mol Cancer. 2024 Jan 10;23(1):12. doi: 10.1186/s12943-023-01901-z.
Malignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and to comprehensively evaluate the practicality of this model in medical research and its feasibility in guiding individualized patient treatment.
MPMOs were constructed using tumor tissue from MPM patients. Histopathological analysis and whole genome sequencing (WGS) were employed to determine the ability of MPMOs to replicate the original tumor's genetic and histological characteristics. The subcutaneous and orthotopic xenograft models were employed to assess the feasibility of establishing an in vivo model of MPM. MPMOs were also used to conduct drug screening and compare the results with retrospective analysis of patients after treatment, in order to evaluate the potential of MPMOs in predicting the effectiveness of drugs in MPM patients.
We successfully established a culture method for human MPM organoids using tumor tissue from MPM patients and provided a comprehensive description of the necessary medium components for MPMOs. Pathological examination and WGS revealed that MPMOs accurately represented the histological characteristics and genomic heterogeneity of the original tumors. In terms of application, the success rate of creating subcutaneous and orthotopic xenograft models using MPMOs was 88% and 100% respectively. Drug sensitivity assays demonstrated that MPMOs have different medication responses, and these differences were compatible with the real situation of the patients.
This study presents a method for generating human MPM organoids, which can serve as a valuable research tool and contribute to the advancement of MPM research. Additionally, these organoids can be utilized as a means to evaluate the effectiveness of drug treatments for MPM patients, offering a model for personalized treatment approaches.
恶性腹膜间皮瘤（MPM）是一种极为罕见且高度侵袭性的肿瘤。由于缺乏能够反映原发性肿瘤生物学特征的准确模型，因此研究 MPM 仍然具有挑战性，且预后极差。本研究旨在利用患者来源的 MPM 类器官（MPMO）建立新的 MPM 临床前模型，并全面评估该模型在医学研究中的实用性及其在指导个体化患者治疗方面的可行性。
从 MPM 患者的肿瘤组织中构建 MPMO。采用组织病理学分析和全基因组测序（WGS）来确定 MPMO 复制原始肿瘤遗传和组织学特征的能力。采用皮下和原位异种移植模型评估建立 MPM 体内模型的可行性。还利用 MPMO 进行药物筛选，并与治疗后患者的回顾性分析结果进行比较，以评估 MPMO 在预测 MPM 患者药物疗效方面的潜力。
我们成功地利用 MPM 患者的肿瘤组织建立了人 MPM 类器官的培养方法，并详细描述了 MPMO 所需的培养基成分。组织病理学检查和 WGS 结果表明，MPMO 准确地再现了原始肿瘤的组织学特征和基因组异质性。在应用方面，利用 MPMO 建立皮下和原位异种移植模型的成功率分别为 88%和 100%。药物敏感性测定表明，MPMO 对药物的反应存在差异，这些差异与患者的真实情况相吻合。
本研究提出了一种生成人 MPM 类器官的方法，该方法可为 MPM 研究提供有价值的研究工具，并有助于推动其进展。此外，这些类器官还可用于评估 MPM 患者药物治疗的效果，为个性化治疗方法提供模型。
