Stem cells grown for medical use often get damaged or lose their properties when produced in large batches, so this project will develop a system to grow them safely and consistently at scale. Many incurable diseases and injuries could be treated by transplanting healthy cells made from human pluripotent stem cells—unspecialised cells that can become any tissue type. But to make this affordable for healthcare systems, researchers need to produce banks of stem cells with different immune profiles, then grow them in large numbers without harming them. Current methods lack reliable ways to monitor cell health during expansion, and damaged cells cannot form healthy tissues. This project will identify which cell properties predict health and stability, then use those markers to improve culture conditions inside an automated cell factory developed by Tokyo Electron. If successful, the validated quality standards and metrics will allow other labs to produce large, consistent batches of healthy stem cells for any patient need. This could eventually enable routine production of replacement tissues for conditions such as Parkinson’s disease, diabetes, or spinal cord injury—turning a promising idea into a practical, scalable manufacturing process.
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Many diseases remain untreatable in spite of advances in medicine world-wide. In recent years there has been much interest in using human pluripotent stem cells (hPSCs), unspecialised cells which can be coaxed using molecules that are found normally in the developing body to produce any cell type. Such stem cells can therefore be used to produce particular repair tissues for patients with different diseases that are so far incurable or for damaged tissues following injury. In order for this to be possible in a manner affordable to our healthcare systems, we need to generate banks of stem cells of different human background which have different immunological tissue types. These can then be used to make desired specialised cells tailored to the patient. However at the moment we do not have reliable ways to grow the cells in large numbers without damaging them, or changing their properties so that they cannot make healthy tissues. In this proposal we will develop the conditions for generating healthy stem cells in large numbers while protecting them from damaging influences. We will generate a system that will be suitable for an automated cell factory so that the cells can be monitored and maintained in pristine stress-free conditions and expanded in a stable way enabling them to in turn generate healthy tissues for the clinic. Such a system has been developed by a company, Tokyo Electron, which now has a base in the UK. We will evaluate a whole series of different properties of these hPSCs and work out which attributes of the cells predict their health and retention of the ability to make more stem cells and form specialised cells. These properies will be compared against commercial and other alternative hPSC test systems and, in the second phase, fed back to further improve culture conditions. In this subsequent second phase we will trial the improved culture conditions with continued cell monitoring for 'good' and 'bad' cell markers in the automated cell factory. The established validated properties will be made available to other researchers so that they can use them to improve their expansion of PSCs and subsequently generate different specialised cell types for different patient needs.
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