Department of Chemistry, University of Toronto, 80 Saint George Street, Toronto, ON, M5S 3H6, Canada.
Princess Margaret Cancer Centre, University Health Network, 610 University Ave., Toronto, ON, M5G 2M9, Canada.
Nat Commun. 2022 Mar 18;13(1):1466. doi: 10.1038/s41467-022-28788-6.
Patient-derived tumor organoids (PDOs) are a highly promising preclinical model that recapitulates the histology, gene expression, and drug response of the donor patient tumor. Currently, PDO culture relies on basement-membrane extract (BME), which suffers from batch-to-batch variability, the presence of xenogeneic compounds and residual growth factors, and poor control of mechanical properties. Additionally, for the development of new organoid lines from patient-derived xenografts, contamination of murine host cells poses a problem. We propose a nanofibrillar hydrogel (EKGel) for the initiation and growth of breast cancer PDOs. PDOs grown in EKGel have histopathologic features, gene expression, and drug response that are similar to those of their parental tumors and PDOs in BME. In addition, EKGel offers reduced batch-to-batch variability, a range of mechanical properties, and suppressed contamination from murine cells. These results show that EKGel is an improved alternative to BME matrices for the initiation, growth, and maintenance of breast cancer PDOs.
患者来源的肿瘤类器官（PDO）是一种极具前景的临床前模型，可重现供体患者肿瘤的组织学、基因表达和药物反应。目前，PDO 培养依赖于基底膜提取物（BME），其存在批次间变异性、异种化合物和残留生长因子的存在，以及机械性能的控制不佳等问题。此外，对于从患者来源的异种移植物中开发新的类器官系，鼠源宿主细胞的污染是一个问题。我们提出了一种用于启动和生长乳腺癌 PDO 的纳米纤维水凝胶（EKGel）。在 EKGel 中生长的 PDO 具有组织病理学特征、基因表达和药物反应，与它们的亲本肿瘤和 BME 中的 PDO 相似。此外，EKGel 提供了降低的批次间变异性、一系列机械性能和抑制来自鼠细胞的污染。这些结果表明，EKGel 是 BME 基质的一种改进替代品，可用于启动、生长和维持乳腺癌 PDO。
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