MAINSTREAM: EPSRC research and partnership hub for health technologies in Manufacturing Stem Cells

Mesenchymal stromal (or stem) cells (MSCs) are adult stem cells that can be easily isolated from the bone marrow or fat tissue. MSCs can turn into bone, cartilage, ligament, tendon and fat-forming cells and so there is a large interest for their use in tissue regeneration. For example, adding MSCs, as a cell therapy, to broken bones or damaged cartilage. With an ageing population where the health of the skeletal system affects the quality of everyday life, this is important. Also, as we age, we can develop diseases that may require transplant procedures. MSCs are immunomodulatory. This means that they can prevent transplant rejection, being used as a drug rather than for their regenerative potential. It is important to note that as MSCs are immunomodulatory, they can be an allogeneic therapy - i.e. cells can be banked by manufacturers and given to different patients, providing an "off-the-shelf" cellular therapy solution. MSCs are also important in the development of cancers, such as blood cancer. As blood cancers develop, the cancer cells signal to MSCs in the bone marrow and the MSCs alter the environment in favour of looking after the cancerous cells rather than healthy blood cells. We propose that MSCs can be delivered to complement chemotherapy, to regenerate healthy bone marrow and look after normal blood cells provided by bone marrow transplants. MSC-based therapies, therefore, hold massive potential to give us more years of high-quality life. However, despite the first MSC-based clinical trial being >25 years ago, the therapies are not commonly used. This is due to the current lack of scalability. NICE looks at new therapies and medicines based on quality-adjusted life years (QALY) and typically views £20k per QALY as cost-effective. The price of MSC therapies is currently much higher than this because we cannot manufacture them efficiently. The problem is that as MSCs proliferate (or grow) in the lab, outside of the body, they age and either stop proliferating or they differentiate in an uncontrolled manner. This means we can only grow relatively few from each donor, keeping the price high through an inability to effectively scale up production and maintain MSCs in an undifferentiated state. The MAINSTREAM EPSRC research and partnership hub for health technologies in Manufacturing Stem Cells for Regenerative Medicine, Immunotherapy and Cancer, will solve this problem and make MSC therapies a reality in the UK and around the world. We have developed materials that tell MSCs to remain as stem cells, to proliferate for longer, to retain their immunomodulatory and regenerative properties and not to age or differentiate in culture. In the hub, we will link these materials and understanding to non-invasive characterisation and manufacturing technologies, so that we can scale-up our materials to an industrial level and study cell phenotype as they grow. To achieve this, it is critical that we link with medical doctors, cell manufacturers and the government. It is paramount that we also link to patients and engaged public to ensure that we focus on user needs and make relevant and usable cell therapies in a responsible manner that regulators and policy-makers are ready for. The hub, and the UK leadership it will provide, will unlock the huge potential of these stem cells to give us not simply more years of life, but years of higher quality life.