The role of Sphingosine 1-phosphate in the Recruitment and Retention of Haematopoietic Stem Cells in the Injured Liver

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Chronic liver disease is an increasing cause of morbidity & mortality in the UK, for which there are limited treatment options. Stem cells within our bone marrow have the ability to migrate to the liver during injury and promote repair, and this has led to the use of stem cell infusions in clinical trials. However, stem cells only enter the liver in small numbers, so if we can better understand the factors that control their entry and retention within the liver, we will be able to improve their use as a therapy for liver disease.We propose that S1P, a naturally occurring chemical within the body, is responsible for regulating the number of stem cells within the liver. We will study the changes of S1P levels that occur in liver disease, and then conduct a series of experiments in which we alter the levels of S1P within the liver to determine what effect this has on the number of stem cells within the liver and also on liver repair. This work will determine whether increasing levels of S1P in the liver increases the number of stem cells in the liver and in turn improves liver repair.