Phase I Trial: Mesenchymal Stem Cells Transplantation in End Stage Liver Disease

Abstract

Background, End-stage liver disease and in particular human liver cirrhosis represents a worldwide health problem. Currently, liver transplant is the only effective treatment, but it is affected by many problems including relative lack of donors, operative damage, risk of rejection and high costs. Stem cell therapy is very attractive in this setting because it has the potential to help tissue regeneration while providing minimally invasive procedures and few complications. The aim of this study was to evaluate the effect of autologous transplantation of bone marrow derived mesenchymal stem cells in cirrhotic patients following chronic hepatitis C virus infection. Methods, Twelve patients with Child C liver cirrhosis, Model of End Stage Liver Disease (MELD) score > 12 were included. They divided into 2 groups according to method of MSCs injection, 1 st group was injected intrasplenic and 2 nd group was injected through the peripheral blood. First group patient's ages ranged from 32 to 69 years, mean value was 48.50 ±11.09, they were 4 males (67%) and 2 females (33%). Second group patient's ages ranged from 43 to 59 years, mean value was 50.83 ±6.88, they were 5 males (83%) and 1 female (17%). Fifty ml bone marrow was aspirated from the iliac bone for separation of MSCs. Surface expression of CD271 and CD34 were analyzed using flowcytometry. Finally approximately 10 million MSCs/ 5ml saline were infused intrasplenic or peripherally in one session. There was highly statistical significant difference between CD271 before and after culture, p value was <0.01. Results, Monthly Follow up of patients for 6 months revealed partial improvement of liver function tests with decline of elevated bilirubin and liver enzymes and elevation of prothrombin concentration and serum albumin levels. There was statistically significant difference between total bilirubin, direct bilirubin, MELD score and creatinine level before and after MSCs injection in both groups, p value was <0.05. Conclusion, MSCs are the most potent component of bone marrow cells in its ability to differentiate into hepatocytes thus, MSC transplantation can be used as a potential treatment for liver cirrhosis. The dose, frequency and route of administration of this treatment are still to be defined.