title: Transplantation of human fetal biliary tree stem/progenitor cells into two patients with advanced liver cirrhosis.
abstract: BACKGROUND
  Efforts to identify cell sources and approaches for cell therapy of liver diseases are ongoing, taking into consideration the limits recognized for adult liver tissue and for other forms of stem cells. In the present study, we described the first procedure of via hepatic artery transplantation of human fetal biliary tree stem cells in patients with advanced cirrhosis.
  
  
  METHODS
  The cells were immune-sorted from human fetal biliary tree by protocols in accordance with current good manufacturing practice (cGMP) and extensively characterized. Two patients with advanced liver cirrhosis (Child-Pugh C) have been submitted to the procedure and observed through a 12 months follow-up.
  
  
  RESULTS
  The resulting procedure was found absolutely safe. Immuno-suppressants were not required, and the patients did not display any adverse effects correlated with cell transplantation or suggestive of immunological complications. From a clinical point of view, both patients showed biochemical and clinical improvement during the 6 month follow-up and the second patient maintained a stable improvement for 12 months.
  
  
  CONCLUSIONS
  This report represents proof of the concept that the human fetal biliary tree stem cells are a suitable and large source for cell therapy of liver cirrhosis. The isolation procedure can be carried out under cGMP conditions and, finally, the infusion procedure is easy and safe for the patients. This represents the basis for forthcoming controlled clinical trials.
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Corso della Repubblica 79, Latina, 04100, Italy. vincenzo.cardinale@uniroma1.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cardinale
authors.affiliation: Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", Rome, 00151, Italy. guido.carpino@uniroma1.it.
authors.forename: Guido
authors.initials: G
authors.lastname: Carpino
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Corso della Repubblica 79, Latina, 04100, Italy. lellons@libero.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Gentile
authors.affiliation: Department of Experimental Medicine, Viale Regina Elena 324, Rome, 00161, Italy. chiara.napoletano@uniroma1.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Napoletano
authors.affiliation: Department of Experimental Medicine, Viale Regina Elena 324, Rome, 00161, Italy. hassan.rahimi@uniroma1.it.
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahimi
authors.affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Via Alfonso Borelli 50, Rome, 00185, Italy. antonio.franchitto@uniroma1.it.|Eleonora Lorillard Spencer-Cenci Foundation, Rome, 00100, Italy. antonio.franchitto@uniroma1.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Franchitto
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Corso della Repubblica 79, Latina, 04100, Italy. rossella.semeraro@gmail.com.
authors.forename: Rossella
authors.initials: R
authors.lastname: Semeraro
authors.affiliation: Department of Experimental Medicine, Viale Regina Elena 324, Rome, 00161, Italy. marianna.nuti@uniroma1.it.
authors.forename: Marianna
authors.initials: M
authors.lastname: Nuti
authors.affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Via Alfonso Borelli 50, Rome, 00185, Italy. paolo.onori@uniroma1.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Onori
authors.affiliation: Department of General Surgery and Organ Transplantation, Viale del Policlinico 155, Rome, 00161, Italy. pasquale.berloco@uniroma1.it.
authors.forename: Pasquale Bartolomeo
authors.initials: PB
authors.lastname: Berloco
authors.affiliation: Department of General Surgery and Organ Transplantation, Viale del Policlinico 155, Rome, 00161, Italy. massimo.rossi@uniroma1.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Department of Experimental Medicine, Viale Regina Elena 324, Rome, 00161, Italy. daniela.bosco@uniroma1.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bosco
authors.affiliation: Department of Gynecologic-Obstetric and Urologic Sciences, Viale Regina Elena 324, Rome, 00161, Italy. roberto.brunelli@uniroma1.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Brunelli
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Corso della Repubblica 79, Latina, 04100, Italy. a.fraveto@gmail.com.
authors.forename: Alice
authors.initials: A
authors.lastname: Fraveto
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Corso della Repubblica 79, Latina, 04100, Italy. cristina.napoli85@gmail.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Napoli
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Corso della Repubblica 79, Latina, 04100, Italy. a.torrice@gmail.com.
authors.forename: Alessia
authors.initials: A
authors.lastname: Torrice
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Corso della Repubblica 79, Latina, 04100, Italy. manuela.gatto@gmail.com.
authors.forename: Manuela
authors.initials: M
authors.lastname: Gatto
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Corso della Repubblica 79, Latina, 04100, Italy. rosanna.venere@gmail.com.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Venere
authors.affiliation: Department of Gynecologic-Obstetric and Urologic Sciences, Viale Regina Elena 324, Rome, 00161, Italy. carlo.bastianelli@uniroma1.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Bastianelli
authors.affiliation: Department of Gynecologic-Obstetric and Urologic Sciences, Viale Regina Elena 324, Rome, 00161, Italy. camilla.aliberti@gmail.com.
authors.forename: Camilla
authors.initials: C
authors.lastname: Aliberti
authors.affiliation: Department of Radiological Sciences, Viale Regina Elena 324, Rome, 00161, Italy. filippomaria.salvatori@uniroma1.it.
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Salvatori
authors.affiliation: Department of Radiological Sciences, Viale Regina Elena 324, Rome, 00161, Italy. luciano.bresadola@uniroma1.it.
authors.forename: Luciano
authors.initials: L
authors.lastname: Bresadola
authors.affiliation: Department of Radiological Sciences, Viale Regina Elena 324, Rome, 00161, Italy. mario.bezzi@uniroma1.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Bezzi
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, 00185, Italy. adolfo.attili@uniroma1.it.
authors.forename: Adolfo Francesco
authors.initials: AF
authors.lastname: Attili
authors.affiliation: Department of Cell Biology and Physiology, Program in Molecular Biology and Biotechnology, UNC School of Medicine, Chapel Hill, NC, 27599, USA. lola.m.reid@gmail.com.
authors.forename: Lola
authors.initials: L
authors.lastname: Reid
authors.affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Via Alfonso Borelli 50, Rome, 00185, Italy. eugenio.gaudio@uniroma1.it.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gaudio
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Corso della Repubblica 79, Latina, 04100, Italy. domenico.alvaro@uniroma1.it.|Eleonora Lorillard Spencer-Cenci Foundation, Rome, 00100, Italy. domenico.alvaro@uniroma1.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Alvaro
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D001659:Biliary Tract / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D016332:Fetal Tissue Transplantation / Q000379:methods*; D006499:Hepatic Artery; D006801:Humans; D008103:Liver Cirrhosis / Q000628:therapy*; D008297:Male; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule