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，但它们与人体器官存在一些内在差异。因此，只有一小部分在实验室开发的药物在临床试验中显示对人体有效。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，我们可以通过直接在人体器官上进行研究来克服这一障碍。这些器官在体外通过一种叫做非原位恒温灌注（NMP）装置保持“活”。NMP设备在临床实践中用于在移植前将供体器官保存在体外。不用于移植的器官被提供给研究。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，例如注射细胞来修复受损的器官（细胞疗法）或测试新的COVID-19药物。重要的是，我们的结果为这种方法的可行性提供了原理证明。同样的方法可以用来进行各种各样的研究，这些研究直到现在都是不可能的，比如在人体组织中测试新的治疗方法。在我们的研究结果发表后，剑桥大学内外的多个团队与我们联系，要求合作并使用这项技术；同时我们获得了UKRI的资助，继续我们在细胞治疗方面的工作。然而，我们最初实验使用的临床设备不能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专用的NMP设备，用于剑桥干细胞研究所（CSCI）的研究。该研究所位于剑桥生物医学研究园区（BRC）内，方便大学内的任何团体访问。BRC结合了两个主要器官移植中心（阿登布鲁克医院和皇家帕普沃斯）的尖端研究设施。该装置将首次使人体器官的多学科研究成为可能。计划使用该设备进行的一些初步研究包括：利用细胞移植修复人体器官以治疗肝脏疾病。为包括COVID-193在内的多种疾病开发和测试药物。用病毒或细菌感染器官，以便更好地了解我们的免疫系统是如何工作的，以及传染性有机体是如何产生抗药性的。探索器官受损后如何再生。开发新的测试方法来预测供体器官在移植后的表现。6. 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研究所和鲁汶天主教大学（比利时），促进国内和国际合作。重要的是，该设备将为开发英国第一批使用NMP器官进行基础研究的设施之一提供基础，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.