A platform facilitating research on human organs maintained ex-vivo.

许多关于人类疾病和我们身体如何工作的研究都是在实验室或使用动物模型进行的。尽管这些系统非常有用，但它们展示了与人体器官的一些内在差异。因此，在实验室开发的药物中，只有一小部分在临床试验中被证明对人体有效。这给英国的研究和医疗保健带来了巨大的金钱、时间和精力负担，并延长了向患者提供有效治疗所需的时间。我们最近证明，通过直接在人体器官上进行研究，我们可以克服这一障碍。这些器官在体外使用称为非原位常温灌流(NMP)装置的机器保持“活着”。NMP设备在临床实践中用于在移植前的一段时间内将供体器官保存在体外。不用于移植的器官被提供用于研究。在我们最近的工作中，我们使用这些器官来试验实验性治疗，例如注射细胞修复受损的器官(基于细胞的治疗)或测试新的新冠肺炎药物。重要的是，我们的结果为该方法的可行性提供了原则证明。同样的方法可以用来进行各种各样的研究，这些研究到目前为止还不可能，比如在人体组织中测试新的疗法。在我们的发现发表后，剑桥大学内外的多个团体与我们接洽，要求合作和使用这项技术；同时，我们获得了UKRI的资金，以继续我们在细胞治疗方面的工作。然而，我们用于初始实验的临床设备无法满足日益增长的研究需求，因为它在日常临床实践中被广泛使用。为了克服这一限制，我们正在申请资金购买一台专门用于研究的NMP设备，该设备将在剑桥干细胞研究所(CSCI)托管。该研究所位于剑桥生物医学研究园区(BRC)内，大学内的任何团体都可以很容易地访问它。BRC将尖端的研究设施与两个主要的器官移植中心(阿登布鲁克医院和皇家帕沃斯)结合在一起。该设备将首次实现对人体器官的多学科研究。使用该设备计划的一些初步研究包括：1.使用细胞移植修复人体器官作为治疗肝病的方法2。开发和测试治疗多种疾病的药物，包括COVID-193。用病毒或细菌感染器官，以更好地了解我们的免疫系统是如何工作的，以及感染性生物是如何对治疗产生抵抗力的。探索器官受损后如何再生5.开发预测捐献器官移植后表现的新测试。6.开发新的生物传感器以实时监测人体器官这些研究将由剑桥大学内外的不同团体进行，包括CSCI、剑桥治疗免疫学和传染病研究所(CITIID)、Wellcome Sanger研究所和(比利时)卢万天主教大学，以促进国家和国际合作。重要的是，该设备将为利用英国的NMP机构开发第一批基础研究设施之一提供基础，为推进国家研究基础设施做出贡献。

Much of the research on human disease and how our body works is performed in the laboratory or using animal models. Although these systems are very useful, they demonstrate some inherent differences from human organs. Consequently, only a small proportion of drugs developed in the laboratory are shown to be effective in human in clinical trials. This results in significant burdens in terms of money, time and effort for UK research and healthcare, and prolongs the period required to deliver effective therapies to patients. We recently demonstrated that we could overcome this barrier by performing studies directly on human organs. These organs were kept 'alive' outside the body using machines called ex-situ normothermic perfusion (NMP) devices. NMP devices are used in clinical practice to preserve donor organs outside the body during the period leading up to a transplantation. Organs not used for transplantation are offered for research. In our most recent work we used these organs to trial experimental treatments, such as injecting cells to repair damaged organs (cell-based therapy) or testing new COVID-19 drugs. Importantly, our results provide proof-of-principle for the feasibility of this approach. The same method could be used to perform a broad variety of studies which were not possible until now, such as testing new therapeutics in human tissue. Following publication of our findings, we were approached by multiple groups within the University of Cambridge and beyond requesting to collaborate and use this technology; while we secured UKRI funding to continue our work on cellular therapy. However, the clinical device we used for our initial experiments could not meet the increased demands for research studies, as it is extensively used in day-to-day clinical practice. To overcome this restriction, we are requesting funding to purchase a dedicated NMP device for research which will be hosted in Cambridge Stem Cell Institute (CSCI). The Institute is located within the Cambridge Biomedical Research Campus (BRC) making it easily accessible to any group within the University. The BRC combines cutting edge research facilities with two major organ transplantation centres (Addenbrooke's Hospital and Royal Papworth). The device will enable for the first time multidisciplinary research in human organs. Some of the initial studies planned using this equipment include:1. Using cell transplantation to repair human organs as a treatment for liver disorders2. Developing and testing drugs for a multitude of diseases including COVID-193. Infecting organs with viruses or bacteria to better understand how our immune system works and how infectious organisms develop resistance to treatment4. Explore how organs regenerate after damage 5. Developing new tests which predict how donor organs will behave after transplantation. 6. Developing new biosensors to monitor human organs in real-timeThese studies will be performed by diverse groups within and beyond the University of Cambridge including the CSCI, the Cambridge Institute of Therapeutic Immunology and Infectious Diseases (CITIID), the Wellcome Sanger Institute and the Catholic University of Louvain (Belgium) promoting national and international collaborations. Importantly, this equipment will provide the foundation for developing one of the first facilities for basic research using NMP organs in the UK contributing to the advancing the national research infrastructure.