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Keywords:

  • bone marrow-derived mesenchymal stem cell;
  • cirrhosis;
  • hepatic fibrosis;
  • liver function;
  • portal hypertension

Abstract

Background

In experimental models, bone marrow-derived mesenchymal stem cells (BM-MSCs) have the capacity to differentiate into hepatocytes and exhibit antifibrotic effects. However, there have been no studies in humans with alcoholic cirrhosis.

Aim

The aim of this study was to elucidate the antifibrotic effect of BM-MSCs in patients with alcoholic cirrhosis, as a phase II clinical trial.

Methods

Twelve patients (11 males, 1 female) with baseline biopsy-proven alcoholic cirrhosis who had been alcohol free for at least 6 months were enrolled. BM-MSCs were isolated from each patient's BM and amplified for 1 month, and 5 × 107 cells were then injected twice, at weeks 4 and 8, through the hepatic artery. One patient was withdrawn because of ingestion of alcohol. Finally, 11 patients completed the follow-up biopsy and laboratory tests at 12 weeks after the second injection. The primary outcome was improvement in the patients’ histological features.

Results

According to the Laennec fibrosis system, histological improvement was observed in 6 of 11 patients (54.5%). The Child-Pugh score improved in ten patients (90.9%) and the levels of transforming growth factor-β1, type 1 collagen and α-smooth muscle actin significantly decreased (as assessed by real-time reverse transcriptase polymerase chain reaction) after BM-MSCs therapy (P < 0.05). No significant complications or side effects were observed during this study.

Conclusions

Bone marrow-derived mesenchymal stem cells therapy in alcoholic cirrhosis induces a histological and quantitative improvement of hepatic fibrosis.