Advanced Xenograft Model with Cotransplantation of Patient-Derived Organoids and Endothelial Colony-Forming Cells for Precision Medicine

精准医疗中患者来源的类器官和内皮集落形成细胞共移植的先进异种移植模型

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作者:Junhye Kwon, Sungryong Oh, Misun Park, Joon Seog Kong, Sunyi Lee, Hyunsook Lee, Younjoo Kim, Kyu-Tae Kang, Ui Sup Shin, Joohee Jung

Abstract

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.

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