title: CD34(+) cell therapy is safe and effective in slowing the decline of hepatic reserve function in patients with decompensated liver cirrhosis.
abstract: OBJECTIVE
  Preclinical studies in rodent models of chronic liver fibrosis have shown that transplantation of peripheral blood (PB) CD34(+) cells leads to hepatic regeneration and a reduction of liver fibrosis by suppressing hepatic stellate cell activity and increasing matrix metalloproteinase activity. The aim of this study was to examine the safety and clinical efficacy of intrahepatic transplantation of autologous granulocyte colony-stimulating factor (G-CSF)-mobilized PB-CD34(+) cells in patients with decompensated liver cirrhosis.
  
  
  METHODS
  PB-CD34(+) cells were isolated from G-CSF-mobilized apheresis products. Ten patients were treated with G-CSF-mobilized PB-CD34(+) cells (treatment group) and seven patients were treated with standard medical therapy. For mobilization, patients in the treatment group received subcutaneous injections of 10 μg G-CSF/kg/day for 5 days. The cells were then injected at three different doses (5 × 10(5) , 1 × 10(6) and 2 × 10(6) cells/kg) through the hepatic artery. Thereafter, all patients were followed up for 24 months.
  
  
  RESULTS
  G-CSF treatment and leukapheresis were well tolerated, and no serious adverse events were observed. Patients in the treatment group had a significant but transient splenomegaly. After 24 weeks, serum albumin was significantly increased in patients who had received middle or high doses of CD34(+) cells compared with baseline. Doppler ultrasound showed a significant increase in hepatic blood flow velocity and blood flow volume after CD34(+) cell therapy. The hepatic vein pressure gradient decreased in two patients who received high-dose CD34(+) cells at week 16.
  
  
  CONCLUSIONS
  CD34(+) cell therapy is feasible, safe and effective in slowing the decline of hepatic reserve function.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan; Liver Cancer Division, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takuji
authors.initials: T
authors.lastname: Torimura
authors.forename: Hideki
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Jyunichi
authors.initials: J
authors.lastname: Kurogi
authors.forename: Hiroto
authors.initials: H
authors.lastname: Inoue
authors.forename: Yukie
authors.initials: Y
authors.lastname: Hori
authors.forename: Shuji
authors.initials: S
authors.lastname: Sumie
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Fukushima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakata
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Abe
authors.forename: Yu
authors.initials: Y
authors.lastname: Ikezono
authors.forename: Osamu
authors.initials: O
authors.lastname: Hashimoto
authors.forename: Takato
authors.initials: T
authors.lastname: Ueno
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Oho
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamura
authors.forename: Seiya
authors.initials: S
authors.lastname: Okuda
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kawamoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ii
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
mesh_terms: D000368:Aged; D018952:Antigens, CD34; D064592:Autografts; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D006499:Hepatic Artery; D055166:Hepatic Stellate Cells / Q000469:parasitology; D006503:Hepatic Veins / Q000503:physiopathology; D006801:Humans; D007279:Injections, Subcutaneous; D008102:Liver Circulation; D008103:Liver Cirrhosis / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008115:Liver Regeneration; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D011446:Prospective Studies; D013812:Therapeutics; D013997:Time Factors; D014690:Venous Pressure
chemical_list: D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor; D020782:Matrix Metalloproteinases
keywords: CD34; cell therapy; decompensated liver cirrhosis; endothelial progenitor cells; granulocyte colony-stimulating factor (G-CSF)