title: Peripheral vein infusion of autologous mesenchymal stem cells in Egyptian HCV-positive patients with end-stage liver disease.
abstract: BACKGROUND
  We have assessed the utility of autologous mesenchymal stem cell (MSC) peripheral vein infusion as a possible therapeutic modality for patients with end-stage liver diseases.
  
  
  METHODS
  Forty patients with post-hepatitis C virus (HCV) end-stage liver disease were randomized into two groups: Group 1 (GI): 20 patients who received granulocyte colony-stimulating factor (G-CSF) for 5 days followed by autologous MSCs peripheral-vein infusion and group 2 (GII): 20 patients who received regular liver-supportive treatment only (control group).
  
  
  RESULTS
  In MSC-infused patients (GI), 54% showed near normalization of liver enzymes and improvement in liver synthetic function. Significant changes were reported in albumin (P = 0.000), bilirubin (P = 0.002), increased international normalized ratio (INR) (P = 0.017), prothrombin concentration (P = 0.029) and alanine transaminase (ALT) levels (P = 0.029), with stabilization of clinical and biochemical status in 13% of cases. None of the patients in GII showed any significant improvement. Hepatic fibrosis was assessed in GI by detection of procollagen IIIC peptide level (PIIICP) and procollagen III N peptide level (PIIINP). The pretreatment values of s-PIIICP and s-PIIINP were 9.4 ± 4.2 and 440 ± 189, respectively, with a decrease to 8.1 ± 2.6 and 388 ± 102, respectively, 3 months after MSC therapy. However, the difference was statistically nonsignificant (P = 0.7). A significant correlation coefficient was reported after 3 months between the s-PIIINP and prothrombin concentration (P = -0.5) and between s-PIIICP and ascites (P = 0.550).
  
  
  CONCLUSIONS
  First, autologous MSC infusion into a peripheral vein is as effective as the previously reported intrahepatic infusion. Second, MSCs have a supportive role in the treatment of end-stage liver disease, with satisfactory tolerability and beneficial effects on liver synthetic functions and hepatic fibrosis. Third, IV infusion of MSCs after G-CSF mobilization improves s-albumin within the first 2 weeks and prothrombin concentration and alanine Taransaminase after 1 month. According to the data from this current study and those previously reported by our group, we recommend further studies on patients' infusion with pure CD133 and CD34 followed by IV infusion of in vitro-differentiated MSCs within 1 week and another infusion after 3 months.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01729221. Registered 17 November 2012.
authors.forename: Hosny
authors.initials: H
authors.lastname: Salama
authors.forename: Abdel-Rahman N
authors.initials: AR
authors.lastname: Zekri
authors.forename: Eman
authors.initials: E
authors.lastname: Medhat
authors.forename: Shereen A
authors.initials: SA
authors.lastname: Al Alim
authors.forename: Ola S
authors.initials: OS
authors.lastname: Ahmed
authors.forename: Abeer A
authors.initials: AA
authors.lastname: Bahnassy
authors.forename: Mai M
authors.initials: MM
authors.lastname: Lotfy
authors.forename: Rasha
authors.initials: R
authors.lastname: Ahmed
authors.forename: Sherief
authors.initials: S
authors.lastname: Musa
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000637:transplantation*; D001854:Bone Marrow Cells; D004534:Egypt; D058625:End Stage Liver Disease / Q000628:therapy* / Q000821:virology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007262:Infusions, Intravenous; D008103:Liver Cirrhosis / Q000628:therapy* / Q000821:virology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D014182:Transplantation, Autologous; D055815:Young Adult
chemical_list: D016179:Granulocyte Colony-Stimulating Factor