Cédric Maerckx1, Tatiana Tondreau1, Silvia Berardis1, Jos van Pelt1, Mustapha Najimi1, Etienne Sokal1. 1. Cédric Maerckx, Tatiana Tondreau, Silvia Berardis, Mustapha Najimi, Etienne Sokal, Laboratory of Pediatric Hepatology and Cell Therapy, Université Catholique de Louvain - Institut de Recherche Expérimentale et Clinique (IRCE), 1200 Brussels, Belgium.
Abstract
AIM: To test the ability of adult-derived human liver stem/progenitor cells (ADHLSC) from large scale cultures to conjugate bilirubin in vitro and in bilirubin conjugation deficient rat. METHODS: ADHLSC from large scale cultures were tested for their phenotype and for their capacity to conjugate bilirubin in vitro after hepatogenic differentiation. In vivo, Gunn rats [uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) deficient animal] were injected with ADHLSC and cryopreserved hepatocytes (positive control). Two, 4, 13 and 27 wk post-transplantation, transplanted Gunn rat bilirubin serum levels were determined by high performance liquid chromatography. Human transplanted cell engraftment was assessed 27 wk post-transplantation using immunohistochemistry and RTqPCR. RESULTS: Large scale culture conditions do not modify ADHLSC phenotype, ADHLSC were able to specifically conjugate bilirubin. ADHLSC were intraportally injected into Gunn rats and blood UCB was measured at different times post-transplantation, infused-Gunn rats exhibited a metabolic effect 3 mo post-transplantation and maintained over a 6 mo period. ADHLSC engraftment into Gunn rat's liver was demonstrated by RTqPCR and immunohistochemistry against albumin and UGT1A1. CONCLUSION: ADHLSC from large scale cultures are efficient in conjugating bilirubin in vitro and in restoring a deficient metabolic function (reducing bilirubin level) in hyperbilirubinemic rats.
AIM: To test the ability of adult-derived human liver stem/progenitor cells (ADHLSC) from large scale cultures to conjugate bilirubin in vitro and in bilirubin conjugation deficient rat. METHODS: ADHLSC from large scale cultures were tested for their phenotype and for their capacity to conjugate bilirubin in vitro after hepatogenic differentiation. In vivo, Gunn rats [uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) deficient animal] were injected with ADHLSC and cryopreserved hepatocytes (positive control). Two, 4, 13 and 27 wk post-transplantation, transplanted Gunn ratbilirubin serum levels were determined by high performance liquid chromatography. Human transplanted cell engraftment was assessed 27 wk post-transplantation using immunohistochemistry and RTqPCR. RESULTS: Large scale culture conditions do not modify ADHLSC phenotype, ADHLSC were able to specifically conjugate bilirubin. ADHLSC were intraportally injected into Gunn rats and blood UCB was measured at different times post-transplantation, infused-Gunn rats exhibited a metabolic effect 3 mo post-transplantation and maintained over a 6 mo period. ADHLSC engraftment into Gunn rat's liver was demonstrated by RTqPCR and immunohistochemistry against albumin and UGT1A1. CONCLUSION: ADHLSC from large scale cultures are efficient in conjugating bilirubin in vitro and in restoring a deficient metabolic function (reducing bilirubin level) in hyperbilirubinemicrats.
Entities:
Keywords:
Gunn rat; Hepatocyte; Liver stem/progenitor cells; Uridine diphosphate-glucuronosyltransferase 1A1; in vitro and in situ differentiation
Authors: Etienne M Sokal; Françoise Smets; Annick Bourgois; Lionel Van Maldergem; Jean-Paul Buts; Raymond Reding; Jean Bernard Otte; Veerle Evrard; Dominique Latinne; Marie Françoise Vincent; Anne Moser; Humberto E Soriano Journal: Transplantation Date: 2003-08-27 Impact factor: 4.939
Authors: Ling-Jia Wang; Yong Ming Chen; David George; Francois Smets; Etienne M Sokal; Eric G Bremer; Humberto E Soriano Journal: Liver Transpl Date: 2002-09 Impact factor: 5.799
Authors: Rolf Schauer; Manfred Stangl; Thomas Lang; Andreas Zimmermann; Alexander Chouker; Alexander L Gerbes; Friedrich W Schildberg; Horst G Rau Journal: J Pediatr Surg Date: 2003-08 Impact factor: 2.545
Authors: Irina V Kholodenko; Leonid K Kurbatov; Roman V Kholodenko; Garik V Manukyan; Konstantin N Yarygin Journal: Cells Date: 2019-09-22 Impact factor: 6.600