Phase i/ii trial of liver derived mesenchymal ...
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Article dans une revue scientifique: Article original
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Title :
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
Author(s) :
Smets, Francoise [Auteur]
Dobbelaere, Dries [Auteur]
Mckiernan, Patrick [Auteur]
Dionisi-Vici, Carlo [Auteur]
Broue, Pierre [Auteur]
Jacquemin, Emmanuel [Auteur]
Lopes, Ana Isabel [Auteur]
Goncalves, Isabel [Auteur]
Mandel, Hanna [Auteur]
Pawlowska, Joanna [Auteur]
Kaminska, Diana [Auteur]
Shteyer, Eyal [Auteur]
Torre, Giuliano [Auteur]
Shapiro, Riki [Auteur]
Eyskens, Francois [Auteur]
Clapuyt, Philippe [Auteur]
Gissen, Paul [Auteur]
Pariente, Daniele [Auteur]
Grunewald, Stephanie [Auteur]
Yudkoff, Marc [Auteur]
Binda, Maria Mercedes [Auteur]
Najimi, Mustapha [Auteur]
Belmonte, Nathalie [Auteur]
Vos, Beatrice De [Auteur]
Thonnard, Joelle [Auteur]
Sokal, Etienne [Auteur]
Dobbelaere, Dries [Auteur]

Mckiernan, Patrick [Auteur]
Dionisi-Vici, Carlo [Auteur]
Broue, Pierre [Auteur]
Jacquemin, Emmanuel [Auteur]
Lopes, Ana Isabel [Auteur]
Goncalves, Isabel [Auteur]
Mandel, Hanna [Auteur]
Pawlowska, Joanna [Auteur]
Kaminska, Diana [Auteur]
Shteyer, Eyal [Auteur]
Torre, Giuliano [Auteur]
Shapiro, Riki [Auteur]
Eyskens, Francois [Auteur]
Clapuyt, Philippe [Auteur]
Gissen, Paul [Auteur]
Pariente, Daniele [Auteur]
Grunewald, Stephanie [Auteur]
Yudkoff, Marc [Auteur]
Binda, Maria Mercedes [Auteur]
Najimi, Mustapha [Auteur]
Belmonte, Nathalie [Auteur]
Vos, Beatrice De [Auteur]
Thonnard, Joelle [Auteur]
Sokal, Etienne [Auteur]
Journal title :
Transplantation
Abbreviated title :
Transplantation
Publication date :
2019-02-18
ISSN :
1534-6080
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases.
This phase I/II prospective, open label, multicenter, randomized trial aimed primarily ...
Show more >Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. 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. 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. 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. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses.Show less >
Show more >Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. 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. 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. 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. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Collections :
Submission date :
2021-09-02T07:01:24Z