Bioengineering a 3D microencapsulated model of breast cancer to reflect tumour microenvironment complexity and disease progression

通过生物工程构建乳腺癌 3D 微胶囊模型，以反映肿瘤微环境的复杂性和疾病进展

• 批准号: 2509711
• 金额: --
• 依托单位: Loughborough University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2509711
• 关键词: Bioengineering; 3D; microencapsulated; model; breast

Drug testing in cancer clinical trials has a drastically low success rate therefore more accurate pre-clinical disease models are urgently needed to translate knowledge gained from basic cancer research to patient benefit. Cancer cell lines cultured on a 2D surface fail to recapitulate the complex 3D tumour microenvironment that contributes to tumourigenesis whilst animal models cannot fully replicate human tumour physiology. Therefore, new 3D pre-clinical cancer models need to be engineered in order to bridge the gap between in vitro and in vivo cancer research. Microencapsulation of cells, where individual cell types or multiple cell types are entrapped within a semi-permeable or solid material to form microcapsules or microspheres, can be used as a 3D cancer model and is amenable for applications in pre-clinical drug testing. This project aims to bioengineer a model of the breast tumour microenvironment using microencapsulation to study the relationship between breast cancer cells and mesenchymal stem cells (MSCs), the role of which has not been fully elucidated in the literature. Membrane emulsification will be employed to produce monodisperse and reproducible microcapsules of biocompatible hydrogels that will be used to encapsulate the two cell types. Membrane emulsification offers advantages over other possible techniques as it is scalable and particle uniformity can be tightly controlled which will allow the study of the impact of microcapsule size on formation of the in vivo model. The importance of microcapsule stiffness and viscoelasticity has also not yet been determined in microencapsulation-based cancer models, therefore hydrogel stiffness will be modulated to represent different stages of disease progression and the effect on cell behaviour and migration will be determined. Importantly, the learning on how to formulate the 'ideal' microcapsule with these specific parameters (e.g. size, material stiffness) will be applicable to the development of other in vivo models and other uses of hydrogel-based microparticles.In summary, membrane emulsification will be used to bioengineer an in vivo-like breast tumour microenvironment that allows the study of the relationship between cancer cells and MSCs and the influence of other environmental factors such as oxygen tension, in a microcapsule format that can be easily adapted for high-throughput drug screening.

癌症临床试验中的药物测试成功率极低，因此迫切需要更准确的临床前疾病模型来将从基础癌症研究中获得的知识转化为患者的利益。在2D表面培养的癌细胞株不能概括复杂的3D肿瘤微环境，而动物模型不能完全复制人类肿瘤生理学。因此，需要设计新的3D临床前癌症模型，以弥合体外和体内癌症研究之间的差距。细胞微囊化，即单个细胞类型或多种细胞类型被包裹在半渗透或固体材料中形成微囊或微球，可用作3D癌症模型，并适用于临床前药物测试。本项目旨在利用微囊化技术构建乳腺肿瘤微环境的生物工程模型，以研究乳腺癌细胞与间充质干细胞之间的关系，目前文献中尚未完全阐明间充质干细胞的作用。膜乳化将被用来生产单分散和可重复的生物相容水凝胶微胶囊，用于包裹这两种类型的细胞。与其他可能的技术相比，膜乳化具有可伸缩性和颗粒均匀度可严格控制的优点，这将使我们能够研究微胶囊大小对体内模型形成的影响。微胶囊硬度和粘弹性的重要性在基于微胶囊的癌症模型中也尚未确定，因此水凝胶硬度将被调节以代表疾病进展的不同阶段，并将确定对细胞行为和迁移的影响。重要的是，学习如何用这些特定的参数(如大小，材料硬度)来形成理想的微囊将适用于其他体内模型的开发和基于水凝胶的微粒子的其他用途。总之，膜乳化将被用于生物工程体内类似乳腺肿瘤的微环境，允许研究癌细胞和间充质干细胞之间的关系以及其他环境因素如氧分压的影响，以一种易于适应高通量药物筛选的微胶囊形式。