Rapid Processing and Drug Evaluation in Glioblastoma Patient-Derived Organoid Models with 4D Bioprinted Arrays
Rapid Processing and Drug Evaluation in Glioblastoma Patient-Derived Organoid Models with 4D Bioprinted Arrays
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DOI：
10.1016/j.isci.2020.101365
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发表时间：
2020-08-21
期刊：
影响因子：
5.8
通讯作者：
Sabaawy, Hatem E.
中科院分区：
文献类型：
--
作者：
Chadwick, Michelle;Yang, Chen;Sabaawy, Hatem E.
胶质母细胞瘤是最常见和致命的原发性脑恶性肿瘤。尽管精准医学肿瘤学（PMO）的进步允许识别胶质母细胞瘤中的分子脆弱性，但治疗选择仍然有限，并且缺乏由基因组和表达谱指导的分子测定，以告知患者参与挽救生命的试验。在这里，我们生成了四维（4D）细胞培养阵列，用于快速评估胶质母细胞瘤患者衍生模型中的药物反应。这些阵列是用热响应形状记忆聚合物（SMP）3D打印的。在加热时，SMP阵列及时地从3D细胞培养插入物自我转化到组织学盒中。我们评估了这些阵列与胶质母细胞瘤细胞、胶质球和患者源性类器官（PDO）模型的效用，并证明了它们与胶质母细胞瘤PDO一起用于评估药物敏感性、靶向活性和药物组合中的协同作用。当包括基因组和药物测试分析时，该平台准备为PMO未来的疗法选择提供快速功能性药物评估。
Glioblastoma is the most common and deadly primary brain malignancy. Despite advances in precision medicine oncology (PMO) allowing the identification of mo-lecular vulnerabilities in glioblastoma, treatment options remain limited, and mo-lecular assays guided by genomic and expression profiling to inform patient enrollment in life-saving trials are lacking. Here, we generate four-dimensional (4D) cell-culture arrays for rapid assessment of drug responses in glioblastoma patient-derived models. The arrays are 3D printed with thermo-responsive shape memory polymer (SMP). Upon heating, the SMP arrays self-transform in time from 3D cell-culture inserts into histological cassettes. We assess the utility of these arrays with glioblastoma cells, gliospheres, and patient derived organoid-like (PDO) models and demonstrate their use with glioblastoma PDOs for assess-ing drug sensitivity, on-target activity, and synergy in drug combinations. When including genomic and drug testing assays, this platform is poised to offer rapid functional drug assessments for future selection of therapies in PMO.