Application of single cell metabolite profiling to optimisation of stem cell bioprocessing

单细胞代谢物分析在干细胞生物加工优化中的应用

• 批准号: BB/K011170/1
• 负责人: Alan Dickson
• 金额: $ 57.52万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK011170%2F1
• 关键词: Application; single; cell; metabolite; profiling

The potential of stem cells as treatments for disease appears in the public arena with increasing frequency. Fundamentally, these are cells that may have the ability to be switched to take on the function of cells within critical roles in the body. Consequently, when the normal cells are damaged, as in heart attacks or paracetamol-induced liver damage, the stem cells should have the ability, as a transplant, to take up the function of the heart or liver cells. The scope exists for stem cell treatments to cure/improve the well-being of patients suffering from life-threatening/-changing conditions. Tremendous advances have been made but a number of key hurdles must be overcome before there is a more complete realisation of the undisputed potential. Chief amongst these is the fact that stem cells do have the potential to take on the functions of many different cell types and the control of this process is not fully understood. Placing this in to the context of our present proposal, the loss of insulin-production by cells of the pancreas generates diabetes. This can be treated by insulin injection, with all the consequences for monitoring and life-style, but the possibility of transplantation of insulin-producing cells to patients offers a vision of cure, rather than therapy. Hence, the key challenge is to understand the processes that control the change from stem cell to a pancreatic cell. This is against a background of stem cells undergoing changes towards many cell types - nerve, liver, muscle, kidney, heart - and generating a mixture of cell types simultaneously. Transplantation of a mixture of cells, rather than the insulin-secreting cell would not be effective. This aspect remains a major limitation for the potential of stem cell therapy to become a reality and it is the focus for this proposal. Our proposal will apply novel approaches to look at stem cells as individual cells using our pancreatic cell lines as a powerful model system. The reason this work is important is that it aims to take "fingerprints" of the metabolism of each cell as an individual entity, enabling us to relate a "fingerprint" with the controlling events that determine if a cell becomes nerve, liver, pancreas etc. The information will aid us to identify processes for maintenance of cells in whatever functional state is desired and to select for cells with a particular functional state. This type of processes can be applied to large-scale generation of cells with defined function - taking the production of cells to the commercial level that will move us towards manufacture of cells in sufficient quantity, as well as quality, to use as real-life medicines. Our approach is one that is unique due to the collaborative positioning of research groups with disruptive new technologies and model cell lines for effective development of a more general technology.

干细胞作为疾病治疗的潜力越来越频繁地出现在公共竞技场。从根本上说，这些细胞可能有能力被转换，以承担身体中关键角色的细胞功能。因此，当正常细胞受损时，如在心脏病发作或对乙酰氨基酚引起的肝损伤中，干细胞应该具有作为移植物的能力，以承担心脏或肝细胞的功能。干细胞治疗存在治愈/改善患有危及生命/改变状况的患者的福祉的范围。已经取得了巨大的进步，但在更全面地实现无可争议的潜力之前，必须克服一些关键障碍。其中最主要的是，干细胞确实有潜力承担许多不同细胞类型的功能，并且对这一过程的控制尚未完全了解。将此置于我们目前建议的背景下，胰腺细胞产生胰岛素的损失产生糖尿病。这可以通过注射胰岛素来治疗，并对监测和生活方式产生所有影响，但将产生胰岛素的细胞移植到患者身上的可能性提供了治愈的前景，而不是治疗。因此，关键的挑战是了解控制从干细胞到胰腺细胞的变化的过程。这是在干细胞经历向许多细胞类型的变化-神经，肝脏，肌肉，肾脏，心脏-并同时产生细胞类型的混合物的背景下。移植混合细胞，而不是胰岛素分泌细胞将是无效的。这方面仍然是干细胞治疗成为现实的潜力的主要限制，这是本提案的重点。我们的建议将采用新的方法来看待干细胞作为一个单独的细胞，使用我们的胰腺细胞系作为一个强大的模型系统。这项工作很重要的原因是，它的目的是采取“指纹”的新陈代谢的每个细胞作为一个单独的实体，使我们能够与“指纹”的控制事件，确定如果一个细胞成为神经，肝脏，胰腺等的信息将帮助我们确定过程中的维护细胞在任何功能状态是理想的，并选择细胞与特定的功能状态。这种类型的过程可以应用于大规模生产具有特定功能的细胞-将细胞的生产带到商业水平，这将使我们朝着制造足够数量和质量的细胞的方向发展，以用作现实生活中的药物。我们的方法是独一无二的，因为研究小组与颠覆性新技术和模型细胞系合作定位，以有效开发更通用的技术。

项目成果

Preservation and stability of cell therapy products: recommendations from an expert workshop.

• DOI: 10.2217/rme-2017-0073
• 发表时间: 2017-07
• 期刊: Regenerative medicine
• 影响因子: 2.7
• 作者: G. Stacey;C. Connon;K. Coopman;A. Dickson;B. Fuller;C. Hunt;P. Kemp;Julie E Kerby;Jennifer Man;P. Matejtschuk;H. Moore;John Morris;R. Oreffo;N. Slater;S. Ward;C. Wiggins;H. Zimmermann