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

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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.