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

基本信息

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
项目类别：
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

项目摘要

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.

概括最近出现了类器官模型，作为一种替代的、更真实的体外表征与传统的 2D 培养方法相比，患者肿瘤。在功能水平上，类器官已被证明可作为用于离体药物测试的真实肿瘤模型。虽然类器官模型通常可以准确地概括肿瘤的空间组织，它们通常是源自单一细胞类型（例如肿瘤细胞或多能干细胞）和现有工具制造具有明确成分的类器官是有限的。为了解决这个问题，我们建议开发用于构建由主要肿瘤、基质和免疫组成的类器官共培养物的仪器先前通过荧光显示细胞类型在多发性骨髓瘤的耐药性中发挥作用标记细胞并将其从患者样本中一步分配到培养孔中。经过监测这些类器官的生长和活力并对它们进行药物测试，我们将确定足以概括主要肿瘤基质的最小功能单元多发性骨髓瘤骨髓生态位的相互作用。如果成功的话，我们设想更加现实源自患者的类器官模型可能会改进功能测定，以测试其敏感性癌症治疗的患者样本，潜在目标是使用这些检测来指导治疗决定。