UKRMP Hub: The Engineered Cell Environment.

Stem cells have great potential in medicine as they can grow into many different cell types in the body. Our aim is to create a research network of scientists and clinicians working towards understanding how stem cells behave within their normal tissue environment. The environment or "Niche" within the body that surrounds stem cells has a profound effect on the behaviour of stem cells and whether they can repair damaged organs. By understanding how the Niche influences stem cells in tissues we aim to use this knowledge to develop future treatments for serious untreatable diseases. To promote "healthy regeneration" in tissues and organs, we will use 2 main strategies: (1) test drugs and small synthetic molecules in experimental models of organ injury. We hope to influence the behaviour of the stem cells within their Niche environment by adding drugs. (2) Another way of treating damaged tissue and organs is to transplant stem cells or cells from stem cells into the damaged organ - this kind of treatment is known as a cell therapy and an example of this used today to treat patients is bone marrow transplantation. Whilst this treatment is successful for many diseases, in some cases this treatment does not work and the cells do not grow well. Our network wants to understand why the Niche environment does not always allow cells to grow well. We hope to develop novel treatments using cell transplantation to promote healthy regeneration of tissue and organs. We aim to develop treatments for patients who are currently suffering from untreatable diseases affecting the (a) liver, (b) joints and the (c) lungs. (a) Liver disease is the 5th most common cause of death in the UK. The current treatment for patients with end-stage cirrhosis and acute liver failure is a liver transplant, however organ availability cannot meet demand and many patients die waiting for an organ. Those who do undergo transplantation require lifelong immunosuppression with concomitant risks of infection, cancer, renal and cardiovascular disease. Thus, there is a clear imperative to identify alternatives treatments. One of our research themes will investigate healthy regeneration of the liver using drugs or cell therapies. (b) Another research theme from our Hub investigates new treatments for Osteoarthritis (OA) which is one of the fastest most rapidly increasing major health conditions, with over 8 million people affected in the UK alone. Whilst end-stage disease is suited to joint replacement, there is an urgent need to address earlier disease stages with repair and regenerative strategies. (c) We are also investigating regeneration of the lung; chronic lung disease is responsible for 6 million inpatient bed days a year in the UK. There is a clear unmet need for this research to be carried out. We will bring together scientists with the different kinds of expertise that we think are required to tackle these scientific and medical challenges. By linking these experts with doctors working in these clinical areas and helping them to collaborate together we hope to make more rapid progress in the development of new treatments for these chronic diseases.