title: Reinfusion of highly purified CD133+ bone marrow-derived stem/progenitor cells in patients with end-stage liver disease: A phase I clinical trial.
abstract: BACKGROUND
  Bone marrow stem/progenitor cells seem to be effective in liver regeneration after tissue injury.
  
  
  OBJECTIVE
  To evaluate the feasibility and safety of the mobilization and reinfusion of CD133+ stem/progenitor cells in patients with end-stage liver disease.
  
  
  METHODS
  Autologous CD133+ stem/progenitor cells, mobilized with granulocyte-colony stimulating factor, were collected by leukapheresis and reinfused at increasing doses through the hepatic artery starting from 5×10(4)/kg up to 1×10(6)/kg.
  
  
  RESULTS
  16 subjects with Model for End-stage Liver Disease (MELD) score between 17 and 25 were enrolled, 14 mobilized an adequate number of CD133+ stem/progenitor cells and 12 were reinfused. No severe adverse events related to the procedure were reported. MELD score significantly worsened during mobilization in Child Turcotte Pugh-C patients. A significant improvement of liver function was observed 2 months after reinfusion (MELD 19.5 vs. 16; P=0.045). Overall, 5 patients underwent liver transplantation within 12 months from reinfusion and 2 died because of progressive liver failure.
  
  
  CONCLUSIONS
  CD133+ stem/progenitor cells reinfusion in patients with end-stage liver disease is feasible and safe. A worsening of liver function was observed during mobilization in Child Turcotte Pugh-C patients. The temporary improvement of MELD score after reinfusion suggests that stem cells therapy may be a "bridge to transplant" approach for these patients.
authors.affiliation: Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy. Electronic address: pietro.andreone@unibo.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
authors.affiliation: Department of Specialty Diagnostic and Experimental Medicine, Bologna University, Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Catani
authors.affiliation: Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Margini
authors.affiliation: Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Brodosi
authors.affiliation: Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Lorenzini
authors.affiliation: Department of Specialty Diagnostic and Experimental Medicine, Bologna University, Bologna, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Sollazzo
authors.affiliation: Department of Specialty Diagnostic and Experimental Medicine, Bologna University, Bologna, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Nicolini
authors.affiliation: Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda, Maggiore Hospital, Milano, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Giordano
authors.affiliation: Department of Regenerative Medicine, Maggiore Hospital, Milano, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Montemurro
authors.affiliation: Department of Specialty Diagnostic and Experimental Medicine, Bologna University, Bologna, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Rizzi
authors.affiliation: Department of Specialty Diagnostic and Experimental Medicine, Bologna University, Bologna, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dan
authors.affiliation: Transfusion Medicine Unit, Bologna University Hospital, Policlinico S. Orsola-Malpighi, Bologna, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Giudice
authors.affiliation: Department of Regenerative Medicine, Maggiore Hospital, Milano, Italy.
authors.forename: Mariele
authors.initials: M
authors.lastname: Viganò
authors.affiliation: Zompatori Radiology Unit, Bologna University Hospital, Policlinico S. Orsola-Malpighi, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Casadei
authors.affiliation: Internal Medicine, Faenza Hospital, Faenza, Italy.
authors.forename: Francesco G
authors.initials: FG
authors.lastname: Foschi
authors.affiliation: "F. Addarii" Institute of Oncology and Transplantation, Bologna University Hospital, Policlinico S. Orsola-Malpighi, Bologna, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Malvi
authors.affiliation: Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Bernardi
authors.affiliation: Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Conti
authors.affiliation: Haematology Clinic, Internal Medicine Department, Genoa University, Genoa, Italy.
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lemoli
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D016022:Case-Control Studies; D058625:End Stage Liver Disease / Q000628:therapy*; D005260:Female; D006023:Glycoproteins; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007558:Italy; D007937:Leukapheresis; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010455:Peptides; D011446:Prospective Studies; D013234:Stem Cells / Q000166:cytology*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D016179:Granulocyte Colony-Stimulating Factor
keywords: Cirrhosis; Haematopoietic stem/progenitor cells; Regenerative medicine; Stem cell therapy