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

慢性肝病是英国发病率和死亡率增加的原因，治疗方案有限。我们骨髓中的干细胞有能力在损伤期间迁移到肝脏并促进修复，这导致在临床试验中使用干细胞输注。然而，干细胞进入肝脏的数量很少，所以如果我们能更好地了解控制它们进入和保留在肝脏内的因素，我们将能够改善它们作为肝病治疗方法的应用。我们认为S1P，一种在体内自然产生的化学物质，负责调节肝脏内干细胞的数量。我们将研究肝脏疾病中S1P水平的变化，然后进行一系列实验，在这些实验中，我们改变肝脏中S1P的水平，以确定这对肝脏中干细胞的数量和肝脏修复有什么影响。这项工作将确定肝脏中S1P水平的增加是否会增加肝脏中干细胞的数量，进而改善肝脏修复。

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.