Kwon Junhye, Oh Sungryong, Park Misun, Kong Joon Seog, Lee Sunyi, Lee Hyunsook, Kim Younjoo, Kang Kyu-Tae, Shin Ui Sup, Jung Joohee
Department of Radiological & Clinical Research, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01812, Republic of Korea.
College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea.
J Oncol. 2021 Jul 13;2021:9994535. doi: 10.1155/2021/9994535. eCollection 2021.
Preclinical evaluation models have been developed for precision medicine, with patient-derived xenograft models (PDXs) and patient-derived organoids (PDOs) attracting increasing attention. However, each of these models has application limitations. In this study, an advanced xenograft model was established and used for drug screening. PDO and endothelial colony-forming cells (ECFCs) were cotransplanted in NRGA mice (PDOXwE) to prepare the model, which could also be subcultured in Balb/c nude mice. Our DNA sequencing analysis and immunohistochemistry results indicated that PDOXwE maintained patient genetic information and tumor heterogeneity. Moreover, the model enhanced tumor growth more than the PDO-bearing xenograft model (PDOX). The PDO, PDOXwE, and clinical data were also compared in the liver metastasis of a colorectal cancer patient, demonstrating that the chemosensitivity of PDO and PDOXwE coincided with the clinical data. These results suggest that PDOXwE is an improvement of PDOX and is suitable as an evaluation model for precision medicine.
已经为精准医学开发了临床前评估模型，其中患者来源的异种移植模型（PDXs）和患者来源的类器官（PDOs）越来越受到关注。然而，这些模型中的每一种都有应用局限性。在本研究中，建立了一种先进的异种移植模型并用于药物筛选。将PDO和内皮集落形成细胞（ECFCs）共移植到NRGA小鼠（PDOXwE）中以制备该模型，该模型也可在Balb/c裸鼠中传代培养。我们的DNA测序分析和免疫组织化学结果表明，PDOXwE保留了患者的遗传信息和肿瘤异质性。此外，该模型比携带PDO的异种移植模型（PDOX）更能促进肿瘤生长。还对一名结直肠癌患者肝转移中的PDO、PDOXwE和临床数据进行了比较，表明PDO和PDOXwE的化学敏感性与临床数据一致。这些结果表明，PDOXwE是对PDOX的改进，适合作为精准医学的评估模型。
