title: The impact of repeated autologous infusion of haematopoietic stem cells in patients with liver insufficiency.
abstract: BACKGROUND
  The worldwide shortage of donor livers has prompted the search for alternative cell therapies. Previous data from our laboratory proved a supportive role for stem cell therapy in the treatment of end-stage liver disease patients. Therefore; this study was conducted to assess the clinical and biochemical effects of repeated stem cell infusion.
  
  
  METHODS
  Ninety patients with liver cirrhosis were randomized to receive either one session treatment (G-I) or two sessions 4 months apart (G-II) of autologous haematopoietic stem cells (HSCs) transplantation and a control group (G-III) who received regular liver treatment. G-CSF was administered to transplanted patients before infusion; HSCs were isolated from 400 cc bone marrow (BM) aspirate. CD34+/CD133+ cells were purified: 50 % of the cells were infused locally in the portal vein on the same day and the other 50 % were differentiated to MSC and infused systemically in a peripheral vein (one session treatment G-I). In G-II, the same process was repeated after 4 months from the first treatment (two session's treatment G-II). Liver function was monitored for 12 months after stem cell therapy (SCT).
  
  
  RESULTS
  Statistically significant improvement was reported in the transplanted patients (G-1) as regards the mean serum albumin, bilirubin and INR levels which started to improve after 2 weeks of treatment and continued to improve till the 6(th) month in the single infusion group. The two sessions infused group (G-II) showed sustained response which continued throughout the all follow-up period (12 month). By the end of the study, 36.7 % of the patients in G-I and 66.7 % in G-II showed improvement in the degree of ascites compared to the control group (G-III). We also reported an improvement in the hepatic functional reserve as assessed by the Child-Pugh and MELD score. Safety of the procedure was evidenced by the low incidence of complications encountered.
  
  
  CONCLUSIONS
  In patients with end-stage liver disease, the repeated infusion with combined routes portal and peripheral veins has a beneficial effect on liver functions with minimal adverse events and more lasting clinical efficacy after repeated HSCs infusion.
authors.affiliation: Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al-Aini st., Fom El-Khaleeg, Cairo, 11976, Egypt. ncizekri@yahoo.com.
authors.forename: Abdel-Rahman N
authors.initials: AR
authors.lastname: Zekri
authors.affiliation: Hepatology and Tropical Medicine Department, El-Kasr Al-Aini School of Medicine, Cairo University, Cairo, 11441, Egypt. hsalama888@yahoo.com.
authors.forename: Hosny
authors.initials: H
authors.lastname: Salama
authors.affiliation: Hepatology and Tropical Medicine Department, El-Kasr Al-Aini School of Medicine, Cairo University, Cairo, 11441, Egypt. dremanmedhat@hotmail.com.
authors.forename: Eman
authors.initials: E
authors.lastname: Medhat
authors.affiliation: Hepatology and Tropical Medicine Department, El-Kasr Al-Aini School of Medicine, Cairo University, Cairo, 11441, Egypt. sheriefmusa@yahoo.com.
authors.forename: Sherief
authors.initials: S
authors.lastname: Musa
authors.affiliation: Hepatology and Tropical Medicine Department, El-Kasr Al-Aini School of Medicine, Cairo University, Cairo, 11441, Egypt. arady_60@hotmail.com.
authors.forename: Hanan
authors.initials: H
authors.lastname: Abdel-Haleem
authors.affiliation: Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al-Aini st., Fom El-Khaleeg, Cairo, 11976, Egypt. ola_sayed@yahoo.com.
authors.forename: Ola S
authors.initials: OS
authors.lastname: Ahmed
authors.affiliation: Hepatology and Tropical Medicine Department, El-Kasr Al-Aini School of Medicine, Cairo University, Cairo, 11441, Egypt. hananahh@hotmail.com.
authors.forename: Hanan Abdel Hafez
authors.initials: HA
authors.lastname: Khedr
authors.affiliation: Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al-Aini st., Fom El-Khaleeg, Cairo, 11976, Egypt. mai_special_micro@yahoo.com.
authors.forename: Mai M
authors.initials: MM
authors.lastname: Lotfy
authors.affiliation: Hepatology and Tropical Medicine Department, El-Kasr Al-Aini School of Medicine, Cairo University, Cairo, 11441, Egypt. gastroserag@gmail.com.
authors.forename: Khaled S
authors.initials: KS
authors.lastname: Zachariah
authors.affiliation: Pathology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt. chaya2000@hotmail.com.
authors.forename: Abeer A
authors.initials: AA
authors.lastname: Bahnassy
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging; D008103:Liver Cirrhosis / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D016179:Granulocyte Colony-Stimulating Factor