PMID- 30801523
OWN - NLM
STAT- MEDLINE
DCOM- 20200608
LR  - 20200608
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 103
IP  - 9
DP  - 2019 Sep
TI  - Phase I/II Trial of Liver-derived Mesenchymal Stem Cells in Pediatric Liver-based 
      Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially 
      Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-derived 
      Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome 
      Patients.
PG  - 1903-1915
LID - 10.1097/TP.0000000000002605 [doi]
AB  - BACKGROUND: Regenerative medicine using stem cell technology is an emerging field 
      that is currently tested for inborn and acquired liver diseases. OBJECTIVE: This 
      phase I/II prospective, open label, multicenter, randomized trial aimed primarily 
      at evaluating the safety of Heterologous Human Adult Liver-derived Progenitor 
      Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or 
      Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary 
      objective included the assessment of safety up to 12 months postinfusion and of 
      preliminary efficacy. METHODS: Fourteen patients with UCDs and 6 with CN syndrome 
      were divided into 3 cohorts by body weight and intraportally infused with 3 doses 
      of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, 
      de novo detection of circulating anti-human leukocyte antigen antibodies, and 
      clinically significant adverse events (AEs) and serious adverse events to 
      infusion were evaluated by using an intent-to-treat analysis. RESULTS: The 
      overall safety of HepaStem was confirmed. For the entire study period, 
      patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious 
      adverse events, of which 38% occurred within 1 month postinfusion. There was a 
      trend of higher events in UCD as compared with CN patients. Segmental left portal 
      vein thrombosis occurred in 1 patient and intraluminal local transient thrombus 
      in a second patient. The other AEs were in line with expectations for catheter 
      placement, cell infusion, concomitant medications, age, and underlying diseases. 
      CONCLUSIONS: This study led to European clinical trial authorization for a phase 
      II study in a homogeneous patient cohort, with repeated infusions and 
      intermediate doses.
FAU - Smets, Francoise
AU  - Smets F
AD  - Department of Paediatrics, Paediatric Gastroenterology and Hepatology Unit, 
      Cliniques Universitaires St Luc, Universite Catholique de Louvain, Brussels, 
      Belgium.
FAU - Dobbelaere, Dries
AU  - Dobbelaere D
AD  - Medical Reference Center for Inherited Metabolic Diseases, University Children's 
      Hospital Jeanne de Flandre and RADEME Research Team for Rare Metabolic and 
      Developmental Diseases, EA 7364, University Lille 2, CHRU Lille, Lille, France.
FAU - McKiernan, Patrick
AU  - McKiernan P
AD  - Liver Unit, Birmingham Children's Hospital, Birmingham, United Kingdom.
FAU - Dionisi-Vici, Carlo
AU  - Dionisi-Vici C
AD  - Department of Hepatology, Gastroenterology and Nutrition, Ospedale Pediatrico 
      Bambino Gesu di Roma, Roma, Italy.
FAU - Broue, Pierre
AU  - Broue P
AD  - Hepatologie pediatrique et maladies hereditaires du metabolisme, Centre de 
      competences maladies hereditaires du metabolisme, Hopital des enfants, CHU 
      Toulouse, France.
FAU - Jacquemin, Emmanuel
AU  - Jacquemin E
AD  - Pediatric Hepatology and Liver Transplantation Unit, Reference Centre for Rare 
      Liver Diseases, CHU Bicetre, Assistance Publique, Hopitaux de Paris, DHU 
      Hepatinov, INSERM 1174, University Paris Sud, Paris, France.
FAU - Lopes, Ana Isabel
AU  - Lopes AI
AD  - Department of Pediatrics, Gastroenterology Unit, Medical Faculty of Lisbon, 
      University Hospital Santa Maria, Lisbon, Portugal.
FAU - Goncalves, Isabel
AU  - Goncalves I
AD  - Hospital Pediatrico de Coimbra, Centro Hospitalar da Universidade de Coimbra, 
      Coimbra, Portugal.
FAU - Mandel, Hanna
AU  - Mandel H
AD  - Department of Pediatrics, Metabolic Unit, Rambam Medical Center, Meyer Children's 
      Hospital, Haifa, Israel.
FAU - Pawlowska, Joanna
AU  - Pawlowska J
AD  - Department of Gastroenterology, Hepatology and Nutritional Disorders, The 
      Children's Memorial Health Institute, Warsaw, Poland.
FAU - Kaminska, Diana
AU  - Kaminska D
AD  - Department of Gastroenterology, Hepatology and Nutritional Disorders, The 
      Children's Memorial Health Institute, Warsaw, Poland.
FAU - Shteyer, Eyal
AU  - Shteyer E
AD  - Department of Pediatrics, Hadassah Ein-Kerem Medical Center, Jerusalem, Israel.
FAU - Torre, Giuliano
AU  - Torre G
AD  - Department of Hepatology, Gastroenterology and Nutrition, Ospedale Pediatrico 
      Bambino Gesu di Roma, Roma, Italy.
FAU - Shapiro, Riki
AU  - Shapiro R
AD  - Liver Transplantation Unit, Institute of Gastroenterology, Schneider Children's 
      Medical Center of Israel, Petach Tikva, Israel.
FAU - Eyskens, Francois
AU  - Eyskens F
AD  - Paediatric department, Universitair Ziekenhuis Antwerpen, Edegem, Belgium.
FAU - Clapuyt, Philippe
AU  - Clapuyt P
AD  - Department of Radiology, Cliniques Universitaires Saint-Luc, Universite 
      Catholique de Louvain, Brussels, Belgium.
FAU - Gissen, Paul
AU  - Gissen P
AD  - GOSH UCL Biomedical Center, UCL Great Ormond Street Institute of Child Health, 
      London, United Kingdom.
FAU - Pariente, Daniele
AU  - Pariente D
AD  - Department of Radiology, CHU Bicetre, Le Kremlin Bicetre, France.
FAU - Grunewald, Stephanie
AU  - Grunewald S
AD  - Centre for Inborn Errors of Metabolism, Great Ormond Street Hospital and 
      Institute of Child Health, UCL, London, United Kingdom.
FAU - Yudkoff, Marc
AU  - Yudkoff M
AD  - Mass Spectroscopy Center, The Children's Hospital of Philadelphia, Philadelphia, 
      USA.
FAU - Binda, Maria Mercedes
AU  - Binda MM
AD  - Promethera Biosciences, Mont-Saint-Guibert, Belgium.
FAU - Najimi, Mustapha
AU  - Najimi M
AD  - Institut de Recherche Experimentale et Clinique, Universite Catholique de 
      Louvain, Brussels, Belgium.
AD  - Promethera Biosciences, Mont-Saint-Guibert, Belgium.
FAU - Belmonte, Nathalie
AU  - Belmonte N
AD  - Promethera Biosciences, Mont-Saint-Guibert, Belgium.
FAU - de Vos, Beatrice
AU  - de Vos B
AD  - Promethera Biosciences, Mont-Saint-Guibert, Belgium.
FAU - Thonnard, Joelle
AU  - Thonnard J
AD  - Promethera Biosciences, Mont-Saint-Guibert, Belgium.
FAU - Sokal, Etienne
AU  - Sokal E
AD  - Department of Paediatrics, Paediatric Gastroenterology and Hepatology Unit, 
      Cliniques Universitaires St Luc, Universite Catholique de Louvain, Brussels, 
      Belgium.
AD  - Promethera Biosciences, Mont-Saint-Guibert, Belgium.
LA  - eng
SI  - EudraCT/2011-004074-28
GR  - U54 HD086984/HD/NICHD NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
SB  - IM
MH  - Adolescent
MH  - Age Factors
MH  - Child
MH  - Child, Preschool
MH  - Crigler-Najjar Syndrome/blood/diagnosis/*drug therapy/physiopathology
MH  - Europe
MH  - Female
MH  - Humans
MH  - Infant
MH  - Liver/*metabolism/pathology/physiopathology
MH  - Liver Regeneration
MH  - *Liver Transplantation/adverse effects
MH  - Male
MH  - Prospective Studies
MH  - *Stem Cell Transplantation/adverse effects
MH  - Time Factors
MH  - Transplantation, Heterologous
MH  - Treatment Outcome
MH  - Urea Cycle Disorders, Inborn/blood/diagnosis/physiopathology/*surgery
EDAT- 2019/02/26 06:00
MHDA- 2020/06/09 06:00
CRDT- 2019/02/26 06:00
PHST- 2019/02/26 06:00 [pubmed]
PHST- 2020/06/09 06:00 [medline]
PHST- 2019/02/26 06:00 [entrez]
AID - 10.1097/TP.0000000000002605 [doi]
PST - ppublish
SO  - Transplantation. 2019 Sep;103(9):1903-1915. doi: 10.1097/TP.0000000000002605.