title: Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: a pilot study.
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.
  
  
  OBJECTIVE
  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 One patient was withdrawn because of ingestion of alcohol.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.
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea; Department of Cell Therapy and Tissue Engineering, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Yoon Ok
authors.initials: YO
authors.lastname: Jang
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Kim
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Eom
authors.forename: Mee Yon
authors.initials: MY
authors.lastname: Cho
authors.forename: Hong Jun
authors.initials: HJ
authors.lastname: Park
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: Kim
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Hyun
authors.initials: H
authors.lastname: Soo Kim
authors.forename: Sang Ok
authors.initials: SO
authors.lastname: Kwon
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Choi
authors.forename: Yong Man
authors.initials: YM
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D001706:Biopsy; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007269:Injections, Intra-Arterial; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D056910:Republic of Korea; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D024042:Collagen Type I; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: bone marrow-derived mesenchymal stem cell; cirrhosis; hepatic fibrosis; liver function; portal hypertension