An off-the-shelf multi-well scaffold-supported platform for tumour organoid-based tissues.
An off-the-shelf multi-well scaffold-supported platform for tumour organoid-based tissues.
复制标题
一个现成的多孔支架支持的平台，用于基于肿瘤类器官的组织。
DOI：
10.1016/j.biomaterials.2022.121883
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发表时间：
2022
期刊：
影响因子：
14
通讯作者：
Li NT
中科院分区：
文献类型：
--
作者：
Li NT
复杂的3D生物工程肿瘤模型提供了更好地捕获患者肿瘤异质性的机会。患者来源的类器官正在成为研究肿瘤异质性和患者反应变化的有用工具。类器官培养通常需要一个3D微环境，可以很容易地制造，以促进筛选。在这里，我们着手创建一个高通量的“现成”平台，该平台允许生成含有类器官的工程微组织，用于标准表型生物测定和基于图像的读数。为了实现这一目标，我们开发了基于类有机体组织的支架植入平台（SPOT）平台。SPOT是一种3D凝胶包埋的体外平台，可以在96或384孔板格式中生产，并能够生成扁平，薄和尺寸限定的微凝胶。SPOT具有很高的应用潜力，因为它具有可重复的制造方法，与现有仪器的兼容性，以及减少样本内和样本间的变化，这可能对数据分析和解释构成挑战。使用SPOT，我们从患者来源的胰腺导管腺癌类器官中产生培养物，并评估对标准治疗化疗化合物的细胞反应，证明我们的平台可用于药物筛选。我们设想96/384-SPOT将提供一个有用的工具来评估患者源性类器官的药物敏感性，并轻松整合到药物发现管道中。
Complex 3D bioengineered tumour models provide the opportunity to better capture the heterogeneity of patient tumours. Patient-derived organoids are emerging as a useful tool to study tumour heterogeneity and variation in patient responses. Organoid cultures typically require a 3D microenvironment that can be manufactured easily to facilitate screening. Here we set out to create a high-throughput, “off-the-shelf” platform which permits the generation of organoid-containing engineered microtissues for standard phenotypic bioassays and image-based readings. To achieve this, we developed theScaffold-supportedPlatform forOrganoid-basedTissues(SPOT)platform. SPOT is a 3D gel-embeddedin vitroplatform that can be produced in a 96- or 384-well plate format and enables the generation of flat, thin, and dimensionally-defined microgels. SPOT has high potential for adoption due to its reproducible manufacturing methodology, compatibility with existing instrumentation, and reduced within-sample and between-sample variation, which can pose challenges to both data analysis and interpretation. Using SPOT, we generate cultures from patient derived pancreatic ductal adenocarcinoma organoids and assess the cellular response to standard-of-care chemotherapeutic compounds, demonstrating our platform's usability for drug screening. We envision 96/384-SPOT will provide a useful tool to assess drug sensitivity of patient-derived organoids and easily integrate into the drug discovery pipeline.