Phase 1 Human Trial of Autologous Mesenchymal Stem Cell Transplantation for the Treatment of Decompensated Cirrhosis.

INTRODUCTION: Liver transplantation is the standard treatment in decompensated cirrhosis; however, it has several limitations including high cost, and several complications. Recent animal works have shown that mesenchymal stem cell (MSC) infusion through the rat tail vein can lead to regression of liver fibrosis. But there has been no human trial of autologous MSC transplantation (Tx) in cirrhosis. The aim of this study was to evaluate safety and feasibility of MSC transplantation in decompensated cirrhosis. In a recent study, infusion of CD 34+ (e.g. hematopoietic stem cells) through the hepatic artery was used to treat cirrhosis. However, we infused MSCs (e.g. non-hematopoietic stem cells) through a peripheral vein.

AIMS & METHODS: After protocol approval by the ethic committee, four patients with decompensated cirrhosis were included. 100 ml of their bone marrow was aspirated and MSCs were cultured. After two months culture, 10 to 70 million MSCs obtained which 95% of the cells were viable (as assessed by trypan blue method) and 95% of the cells were morphologically and immunophenotypically MSCs. The MSCs were infused through a peripheral vein. Outcomes were changes in liver function tests, MELD score, and liver volume (as measured by CT volumetry) 5 months after Tx. During follow up, patients’ medications (e.g duretics, or propranolol) remained the same as before MSCs Tx.

RESULTS: Four patients (1 male, 3 female) aged 30 to 56 were included. The etiology of cirrhosis was autoimmune hepatitis or cryptogenic. The follow up for the first patient has been completed, and other 3 patients have 2.5 to 4 months of follow up. In first patient, PT (18.5 to 13 seconds), and albumin (2.9 to 3.8 g/dL) normalized, and MELD score was decreased from 16 to 11. Her liver volume increased from 495 to 815 ml. In patient 2, PT decreased from 20.1 to 17.5. In patient 3, PT decreased from 19.1 to 15.7 seconds, and MELD score decreased from 17 to 14. Patient 4 has not yet been shown any significant improvement in liver function tests. The procedure was safe, and there was no any adverse effect.

CONCLUSION: MSCs Tx is a novel approach to treat cirrhosis. For the first time, we showed that this procedure is safe and feasible, and signs of improvement found in some of our patients are promising.