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
Year: 2019
Type: article
Abstract: 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.
Source: Transplantation
Authors: Françoise Smets, Dries Dobbelaere, Patrick McKiernan, Carlo Dionisi-Vici, Pierre Broué, Emmanuel Jacquemin, Ana Isabel Lopes, Isabel Gonçalves, Hanna Mandel, Joanna Pawlowska, Diana Kamińska, Eyal Shteyer, Giuliano Torre, Riki Shapiro, François Eyskens, Philippe Clapuyt, Paul Gissen, Danièle Pariente, Stephanie Grunewald, Marc Yudkoff, Maria Mercedes Binda, Mustapha Najimi, Nathalie Belmonte, Beatrice de Vos, Joelle Thonnard, Etienne Sokal
Institutions: Cliniques Universitaires Saint-Luc, UCLouvain, Centre Hospitalier Universitaire de Lille, Hôpital Jeanne de Flandre, Maladies RAres du DEveloppement embryonnaire et du MEtabolisme, Birmingham Children's Hospital, Bambino Gesù Children's Hospital, Centre Hospitalier Universitaire de Toulouse, Hôpital des Enfants, Inserm, Assistance Publique – Hôpitaux de Paris, Bicêtre Hospital, Hospital de Santa Maria, Unidade Local de Saúde de Coimbra, University of Coimbra, Rambam Health Care Campus, Meyer Children's Hospital, Children's Memorial Health Institute, Hadassah Medical Center, Schneider Children's Medical Center, Antwerp University Hospital, Great Ormond Street Hospital, University College London, Children's Hospital of Philadelphia, Promethera Biosciences (Belgium)
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2918249641