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The review article by Kallies et al focuses on the various relationships between bone marrow stem cells (BMSC) and liver diseases (Gut 2007;56:716–24). It discusses experimental studies with animal models and critically examines the possible role of BMSC in liver repair through the delivery of growth factors, fibrosis resolution and new blood vessel formation.
In addition, the authors examine the development of BMSC treatment of liver diseases and describe three uncontrolled phase 1 clinical trials in humans published up to December 2006. The main end point of these trials was to evaluate the feasibility and safety of BMSC treatment in patients with chronic liver disease. In one trial, human CD34+ stem/progenitor cell populations mobilised into the blood by granulocyte colony‐stimulating factor were injected directly into the portal vein or hepatic artery.1 The study from Terai et al transplanted autologous BMSC that were prepared from a large amount (400 ml) of iliac crest aspirate and infused into the peripheral vein of the patients.2 Feasibility and safety was observed in all studies. Patients' follow‐up showed improvement of serum albumin levels and Child–Pugh score.
Our research group has recently published data on 10 patients on a waiting list for a liver transplant who had end‐stage chronic liver disease and were enrolled to receive infusion of autologous BMSC.3 About 50 ml of bone marrow was aspirated under mild sedation and prepared by centrifugation in a Ficoll–Hypaque gradient. A minimum of 100 millions of mononuclear‐enriched bone marrow cells were infused into the hepatic artery of the patients by the routine technique used for arterial chemoembolisation of liver tumours. Our results showed that infusion of BMSC into the hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, we also observed a decrease of serum bilirubin and an increase in albumin levels.
It seems clear that trials of BMSC treatment in patients with liver disease are still at a preliminary stage and a better understanding of the physiology and mechanism of action of BMSC in animal models of liver disease is needed. Nevertheless, the high death rate of patients on a waiting list for a liver transplant, especially in some areas of the world, and the fact that autologous BMSC treatment is feasible, safe and seems to lead to improvement of the Child–Pugh score and serum albumin levels suggests that randomised controlled studies should be carried out to evaluate the efficacy of BMSC treatment in patients with advanced liver disease.