Stem cell therapy in liver disease

[摘要] Liver cirrhosis is the fifth leading cause of death worldwide and the definitive treatment for liver cirrhosis is liver transplantation although there are limitations such as organ availability and surgical risks. Therefore, alternative therapies have been studied extensively and stem cell therapies have shown some promising results although most studies are small and not randomised. The aim of this thesis was to explore the effectiveness of stem cell therapy in patients with chronic liver disease as well as explore the mechanism behind fibrosis resolution achieved with cell therapy. There were three parts to the thesis: firstly, I examined the mechanistic actions behind fibrosis reduction by the infusion of bone marrow derived haematopoietic stem cells (HSC) in mice chronic fibrosis liver injury model. I worked on both immune-histochemical staining and qPCR to measure the effect oval cell response, matrix metalloproteinases and macrophage subsets within the liver with HSC therapies. Secondly, I recruited patients with chronic liver diseases for a multicentre, randomised, controlled trial to assess the clinical effectiveness of either subcutaneous granulocyte-colony stimulating factor (GCSF) or GCSF with repeated HSC infusions. The co-primary outcomes were improvement in severity of liver disease measured by model for end stage live disease (MELD) at 3 months and the trend of MELD change over time. The results showed that neither of the treatments improved the clinical outcomes. Lastly, I performed a systematic review of current published studies of stem cells therapies in liver diseases. The results showed that stem cells improved patients’ clinical parameters in the short term (<6 months) but had no benefit on long term outcomes. In conclusion, bone marrow derived stem cell therapy did not seem to be effective in liver cirrhosis.

[发布机构] University:University of Birmingham;Department:Institute of Immunology and Immunotherapy

[关键词] Q Science;QR Microbiology;QR180 Immunology