Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: a pilot study

Liver Int. 2014 Jan;34(1):33-41. doi: 10.1111/liv.12218. Epub 2013 Jun 19.

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 × 10(7) 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 One patient was withdrawn because of ingestion of alcohol.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.

Trial registration: ClinicalTrials.gov NCT01741090.

Keywords: bone marrow-derived mesenchymal stem cell; cirrhosis; hepatic fibrosis; liver function; portal hypertension.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Adult
  • Biopsy
  • Cells, Cultured
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Injections, Intra-Arterial
  • Liver / metabolism
  • Liver / pathology*
  • Liver Cirrhosis, Alcoholic / metabolism
  • Liver Cirrhosis, Alcoholic / pathology
  • Liver Cirrhosis, Alcoholic / surgery*
  • Male
  • Mesenchymal Stem Cell Transplantation* / adverse effects
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • RNA, Messenger / metabolism
  • Republic of Korea
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • ACTA2 protein, human
  • Actins
  • Collagen Type I
  • RNA, Messenger
  • TGFB1 protein, human
  • Transforming Growth Factor beta1

Associated data

  • ClinicalTrials.gov/NCT01741090