Effect of Mesenchymal Stem Cells-derived Exosomes in Decompensated Liver Cirrhosis

Overview

Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. However, little is known about MSC-exosome therapy. We will evaluate the therapeutic potential of mesenchymal stem Cell-Exosomes as an alternative to cell therapy in Cirrhotic patients. This study examined the safety and efficacy of umbilical cord-derived MSC-exosomes in patients with decompensated LC.

Liver fibrosis is the major cause of morbidity and mortality in patients with liver disorders. Liver fibrosis can be reverted with the removal of the underlying etiology. However, if chronic inflammation and injury persist, liver fibrosis is likely to progress to liver cirrhosis (LC). LC is generally characterized by the formation and accumulation of an extracellular matrix, which lead to the progressive distortion of the hepatic architecture. LC usually progresses irreversibly into a decompensated stage, which is characterized by a series of clinical manifestations, including ascites, variceal hemorrhage, and hepatic encephalopathy, while ascites is the most common clinical symptom in such patients. Although ascites might be treated with diuretics, periodic paracentesis, or a transjugular intrahepatic portosystemic shunt, liver transplantation is the only option that can improve the survival of these patients. However, the severe shortage of donor livers, high costs, and potential serious complications have restricted the availability of liver transplantation worldwide. Therefore, alternative strategies are under intense investigation. Mesenchymal stem cells (MSC) have self-renewal abilities and multidirectional differentiation potentials. They also interact with various types of immune cells, leading to immunomodulation. MSCs have been used therapeutically in clinical trials for graft-versus-host disease and appear to be effective in immune-mediated tissue injury, transplantation, and autoimmunity. In particular, MSCs have also been used to treat liver diseases in animal models and patients. Studies from animal models have shown that bone marrow-derived MSC (BM-MSC) infusion ameliorates liver fibrosis and reverses fulminant hepatic failure. In clinical trials, autologous MSC infusion has been demonstrated to be safe, feasible and can improve the liver function of some LC patients. In addition, BM-MSC from patients with chronic HBV infection suffer from proliferative deficiency and might not be the best choice. In contrast, human umbilical cord-derived MSC (UC-MSC) are free from these limitations related to autologous BM-MSC. In addition, UC-MSC can be obtained from the discarded UC, and therefore, can be produced on a large scale. It has been reported that human UC-MSC infusion can improve liver fibrosis in rats. It has been shown that UC-MSC have potential to be used in clinical scenarios for the treatment of human liver diseases. In the present study, the investigators examine the safety and efficacy of UC-MSC derived exosomes in decompensated LC patients. 15 enrolled patients will receive standard medication plus MSC-derived exosomes at a final dose of 40mg in three weeks.