Developing stem cell therapies for the treatment of inherited and acquired liver disease

基于干细胞的方法很可能是未来开发许多疾病新疗法的关键，范围从更换或修复受损伤或衰老影响的器官，到改变身体对损伤的自身反应的方法，这些损伤在失控时可能会产生持久的破坏性影响。该项目将支持伯明翰大学(UOB)和广州生物医学与健康研究所(GIBH)之间的一项研究倡议，该倡议旨在开发基于干细胞的新型疗法。GIBH在基础干细胞生物学领域拥有强大的国际声誉，而大华大学在细胞疗法的开发及其临床试验测试方面拥有无与伦比的经验。这一倡议将成为最高级别的国际研究合作的典范，每个机构都能从彼此的专业知识和专家资源中获益，从而能够交付尖端研究成果，目的是将发现迅速转化为患者的利益。这一试点项目将重点开发以干细胞为基础的手段，以应对广泛的肝病。肝病是现代社会发病率和死亡率的主要原因。在英国，慢性肝病的患病率在0.76-1%之间，是英格兰和威尔士的第五大杀手，也是前五名中唯一一种仍在逐年上升的疾病。其中大部分与酒精、病毒或肥胖造成的慢性肝损伤有关，但也包括急性(扑热息痛)损伤或自身免疫破坏造成的肝损伤。在中国身上，肝病的情况更是令人担忧。从历史上看，这反映了乙肝的感染，尽管肥胖导致的慢性肝病现在正在上升。此外，一些遗传特征会影响肝功能，导致代谢紊乱。对于这些疾病中的许多，除了肝脏移植之外，还没有有效的治疗方法。该项目将探索如何将诱导的多能干细胞(IPSCs)用于治疗肝脏疾病的各种方式。IPSCs可以由任何容易获得的细胞制成，例如来自皮肤，并具有无限维持和扩张的潜力。同时，IPSCs可以转化为细胞类型，作为受损组织的替代物，或者转化为具有其他有用治疗特性的特定细胞类型。GIBH是IPSCs生成的世界领先者，并将与UOB团队联手生产和测试与肝病治疗相关的两种不同类型的细胞。首先是肝细胞(肝细胞)，伯明翰研究小组在制造f(从人类胚胎干细胞)和在肝损伤动物模型中测试方面拥有专业知识。第二种细胞类型是间充质基质细胞(MSCs)，它能够抑制人体自身对某些损伤的夸大炎症反应，如果不加以控制，可能会导致长期损害。除了建立和共享肝细胞和MSCs的生成和测试方案外，该项目还将为建立共享细胞库奠定基础，这将为更广泛的研究铺平道路。尤其值得一提的是，该项目将成为一种更加个性化的干细胞治疗方法的资源，因为IPSCs将来自具有不同遗传背景的广泛个人，包括一些定义了影响肝功能的遗传缺陷的人。总体而言，拟议中的项目将为伯明翰和广州两地相关机构之间的联合研究实验室和干细胞库奠定基础，并有望开发新的概念和治疗可能性，使英国人和中国受益。

Stem cell based approaches are likely to be key in the future development of novel therapies for many diseases ranging from the replacement or repair of organs affected by injury or the effects of ageing through to ways to modify the body's own responses to injury, which can have lasting damaging effects when out of control. This project will underpin a research initiative between the University of Birmingham (UoB) and the Guangzhou Institute of Biomedicine and Health (GIBH) that seeks to develop novel stem cell based therapies. GIBH has a strong international reputation in fundamental stem cell biology, while UoB has unrivalled experience in the development of cell-based therapies and their testing in clinical trials. This initiative will be a model for international research collaboration at the highest level, each institution gaining from the other's expertise and specialist resources to enable delivery of cutting-edge research outcomes with the objective to translate discoveries rapidly into patient benefit. This pilot project will focus on the development of stem cell-based means to tackle a wide range of liver diseases. Liver disease is a major cause of morbidity and mortality in modern societies. In the UK the prevalence of chronic liver disease is between 0.76-1% and represents the fifth 'big killer' in England & Wales, and is the only disease in the top 5 that is still increasing year-on-year. The majority of this relates to chronic liver damage due to alcohol, viruses or obesity, but also includes liver damage resulting from acute (paracetamol) injury or autoimmune destruction. The situation of liver disease is even more alarming in China. Historically this reflected Hepatitis B infection, although chronic liver disease due to obesity is now rising. In addition, a number of inherited traits impact on liver function resulting in metabolic disorders. For many of these diseases there is no effective treatment, except liver transplantation.The project will explore how induced pluripotent stem cells (iPSCs) can be utilised in a variety of ways in the treatment of liver diseases. iPSCs can be made from any readily available cells, such as from the skin, and have the potential to be maintained and expanded indefinitely. At the same time iPSCs can be converted into cell types to act as replacements for damaged tissue or into specific cell types with other useful therapeutic properties. GIBH are world leaders in the generation of iPSCs, and will join forces with the UoB team to produce and test two different cell types from them that have relevance in the treatment of liver disease. The first will be liver cells (hepatocytes), which the Birmingham team has expertise in producing f(from human embryonic stem cells) and testing in animal models of liver damage. The second cell type are mesenchymal stromal (or stem) cells (MSCs), which have the ability to dampen the body's own exaggerated inflammatory response to certain injuries, which if left unchecked can itself result in long term damage.In addition to setting up and sharing protocols for the generation and testing of hepatocytes and MSCs, this project will also lay the groundwork for the establishment of a shared cell 'bank' that will pave the way for more extensive research. In particular, it will act as a resource for a more 'personalised' approach to stem cell-based therapy since iPSCs will be made from a wide range of individuals with different genetic backgrounds, including some who have defined inherited genetic defects that impact upon liver function.Overall, the proposed project will contribute to the foundation for a joint research laboratory and a stem cell bank between the involved institutions of Birmingham and Guangzhou, and is expected to develop new concepts and therapeutic possibilities that will benefit people from the UK and China.