文章基本信息

标题：Rapid Processing and Drug Evaluation in Glioblastoma Patient-Derived Organoid Models with 4D Bioprinted Arrays
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作者：Michelle Chadwick ; Chen Yang ; Liqiong Liu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：8
页码：1-32
DOI：10.1016/j.isci.2020.101365
语种：English
出版社：Elsevier
摘要：SummaryGlioblastoma is the most common and deadly primary brain malignancy. Despite advances in precision medicine oncology (PMO) allowing the identification of molecular vulnerabilities in glioblastoma, treatment options remain limited, and molecular 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 assessing 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.Graphical AbstractDisplay OmittedHighlights•4D printed thermo-responsive polymer arrays self-transform for 3D culture and histology•Patient-derived organoid models represent original tumors better than spheres in arrays•Cellular heterogeneity and drug responses are assessed in glioblastoma organoid models•Functional utility is shown by detecting drug sensitivity, on-target activity, and synergyTissue Engineering; Medical Biotechnology; Cancer