Building microenvironment-containing organoids from patient samples with single-cell precision

以单细胞精度从患者样本中构建含有微环境的类器官

• 批准号: 10225309
• 负责人: SCOTT R MANALIS
• 金额: $ 20.67万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10225309
• 关键词: Address; Architecture; Behavior; Biological Assay; Biopsy Specimen; Bone Marrow; Bone marrow biopsy; Brightfield Microscopy; Cell Line; Cell Separation; Cells; Clinic; Coculture Techniques; Drug resistance; Fluorescence; Goals; Growth; Immune; Immunofluorescence Microscopy; Immunomodulators; In Vitro; Individual; Label; Lead; Logic; Malignant Neoplasms; Modeling; Monitor; Multiple Myeloma; Natural Killer Cells; Organoids; Patients; Play; Pluripotent Stem Cells; Population; Predisposition; Protocols documentation; Recovery; Role; Sampling; Sorting - Cell Movement; Standardization; Stress; Technology; Testing; Therapeutic; Time; Tissues; base; cell immortalization; cell type; design; drug sensitivity; drug testing; improved; instrument; neoplastic cell; tool; tumor

Summary Organoid models have recently emerged as an alternative, more realistic in vitro representation of patient tumors when compared to traditional 2D culture approaches. At a functional level, organoids have proven useful as realistic tumor model to be used for ex vivo drug testing. Although organoid models can often accurately recapitulate the spatial organization of the tumor, they are typically derived from a single cell type (e.g., tumor cells or pluripotent stem cells) and existing tools for making organoids with well-defined compositions are limited. To address this, we propose to develop an instrument for building organoid co-cultures consisting of the major tumor, stromal, and immune cell types previously shown to play a role in drug resistance in multiple myeloma, by fluorescently labeling cells and dispensing them from patient samples into culture wells in a single step. By monitoring the growth and viability of these organoids and subjecting them to drug testing, we will determine the minimal functional unit that is sufficient to recapitulate the major tumor-stroma interactions of the multiple myeloma bone marrow niche. If successful, we envision that more realistic patient-derived organoid models could lead to improved functional assays to test the susceptibility of patient samples to cancer therapeutics, with the potential goal of using these assays to guide treatment decisions.

概括 器官模型最近已成为一种替代，更现实的体外表示 与传统的2D培养方法相比，患者肿瘤。在功能水平上，器官 被证明可作为现实的肿瘤模型，可用于离体药物测试。虽然是器官 模型通常可以准确地概括肿瘤的空间组织，通常是 源自单个细胞类型（例如肿瘤细胞或多能干细胞）和现有工具 用明确的组成制作类器官是有限的。为了解决这个问题，我们建议开发 建立由主要肿瘤，基质和免疫培养的类和培养的仪器 先前证明的细胞类型在多发性骨髓瘤中发挥作用，荧光 将细胞标记并将其从患者样品中分配到一个步骤中。经过 监测这些类器官的生长和生存能力并使它们接受药物测试，我们将 确定足以概括主要肿瘤的功能单位 多发性骨髓瘤骨髓生态位的相互作用。如果成功，我们会设想更现实的 患者衍生的类器官模型可能会导致功能测定改善，以测试 患者样品进行癌症治疗剂，其潜在目标是使用这些测定法进行指导 治疗决定。