Microbiome-Bone Chip

微生物组-骨芯片

• 批准号: EP/Y001842/1
• 负责人: Stefaan Verbruggen
• 金额: $ 14.97万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY001842%2F1
• 关键词: Microbiome; Bone; Chip

The recent recognition of the central role played by the microbiome in human health has lead to a paradigm shift in medicine, with ever-increasing awareness of how these host-specific communities of microorganisms can affect patient health. In the past decade, the gut microbiome has emerged as a contributor to disease processes throughout the body, but only recently has been shown to influence orthopaedic biomechanics. Early findings suggest that the microbiome may help answer questions in orthopaedic biomechanics that are not well addressed by current interventions and highlight the promise of the emerging field of "Musculoskeletal Microbiology".To date, analysis of gut-microbiome crosstalk has almost exclusively relied on the genomic or metagenomic analysis of samples collected from humans or animals. This is because no method exists to establish stable complex communities of gut commensal microorganisms in direct contact with intestinal epithelium and its overlying mucus layer in vitro. Although animal models have been used to analyse host-microbiome interactions and their contributions to pathophysiology, there are no in vitro systems available to verify these interactions in human cells cultured with a complex human microbiome. Thus, there is a great unmet need for experimental models that can sustain complex populations of human aerobic and anaerobic microbiota in contact with living human tissues to analyse dynamic and physiologically relevant human host-microbiome interactions.This project will bring together the Organ-on-a-Chip technology applied by Dr Verbruggen to develop a bone-chip model, with microbiome cultures and metabolomic data from an animal model developed by a founder of this new field of Musculoskeletal Microbiology, Prof Hernandez. With industrial support from the leading manufacturer of organ-chip technology, Emulate, and on-site expertise in 3D models of the microbiome, from Co-Investigator Dr Krishna Kumar, this project will build a proof-of-concept multi-organ chip system that links the gut microbiome with a bone-chip model. This chip model will provide a leap forward in drug discovery by providing a precision model to pick apart the important biological mechanisms, as well as providing a new technology to speed up drug testing while using less animals.

最近认识到微生物组在人类健康中发挥的核心作用，导致了医学的范式转变，人们越来越意识到这些宿主特异性微生物群落如何影响患者健康。在过去的十年中，肠道微生物组已经成为全身疾病过程的一个贡献者，但直到最近才被证明会影响骨科生物力学。早期的研究结果表明，微生物组可能有助于回答骨科生物力学中目前干预措施没有很好解决的问题，并突出了新兴领域“肌肉骨骼微生物学”的前景。迄今为止，肠道微生物组串扰的分析几乎完全依赖于从人类或动物收集的样本的基因组或宏基因组分析。这是因为没有方法在体外建立与肠上皮及其上覆粘液层直接接触的稳定的肠道微生物复合群落。虽然动物模型已被用于分析宿主-微生物组相互作用及其对病理生理学的贡献，但没有体外系统可用于验证与复杂的人类微生物组一起培养的人类细胞中的这些相互作用。因此，对于能够维持复杂的人体需氧和厌氧微生物群与活体人体组织接触的实验模型，以分析动态和生理相关的人体宿主-微生物群相互作用，存在巨大的未满足的需求。该项目将结合Verbruggen博士应用的器官芯片技术，开发骨芯片模型，肌肉骨骼微生物学这一新领域的创始人埃尔南德斯教授开发的动物模型的微生物组培养和代谢组学数据。在领先的器官芯片技术制造商Emulate的工业支持下，以及共同研究者Krishna Kumar博士在微生物组3D模型方面的现场专业知识，该项目将建立一个概念验证的多器官芯片系统，将肠道微生物组与骨芯片模型联系起来。这种芯片模型将通过提供一个精确的模型来挑选重要的生物机制，并提供一种新技术来加快药物测试，同时使用更少的动物，从而在药物发现方面实现飞跃。