As cells grow in culture (and in our bodies), they age. Growth and regenerative activity places stress on cells and they accumulate damage and, eventually, become senescent. Senescence is when a cell stops growing – but it is more than this. MAINSTREAM focusses on the growth of mesenchymal stromal cells (MSCs). These cells are multipoint stem cells and can act to help regenerate cartilage and bone. They are also anti-inflammatory and immunomodulatory. This means that MSCs can help the body to regenerate or heal not just through making new tissue but by helping other cells around them to heal damage through making the environment better for surrounding cells. To do this, they secrete signals that stop inflammation and prevent rejection – that is that they secrete these signals when they are young! As they approach Senescence through long-term growth, they start to secrete molecules that aggravate inflammatory and immune cells and thus reduce regeneration. 

MSCs are a cell type that can underpin many regenerative strategies, both directly, in terms of new bone and cartilage, and indirectly, helping other cells. However, to achieve this, we need to be able to take them out of the body and grow them to large numbers while avoiding cell ageing and senescence. Only when we can do this will we be able to manufacture enough good MSCs that are affordable as therapies.

In MAINSTREAM, we are developing materials technologies that support MSCs to grow, but that control stress pathways to prevent senescence. These materials mimic aspects of their natural homes in our bodies – they match the viscoelasticity and shape of their homes, such as the bone marrow. We are also developing the tools (sensors, microscopies) to study cell ageing in culture.

Success in developing these materials and sensing technologies will open up MSCs as a regenerative cell therapy in musculoskeletal regeneration, but also in transplantation, where we want other cells and tissues to be protected from the immune system.