title: Human liver stem/progenitor cells decrease serum bilirubin in hyperbilirubinemic Gunn rat.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Cédric
authors.initials: C
authors.lastname: Maerckx
authors.affiliation: 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.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Tondreau
authors.affiliation: 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.
authors.forename: Silvia
authors.initials: S
authors.lastname: Berardis
authors.affiliation: 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.
authors.forename: Jos
authors.initials: J
authors.lastname: van Pelt
authors.affiliation: 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.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Najimi
authors.affiliation: 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.
authors.forename: Etienne
authors.initials: E
authors.lastname: Sokal
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D004195:Disease Models, Animal; D015536:Down-Regulation; D014453:Glucuronosyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism* / Q000637:transplantation*; D006801:Humans; D007024:Hypotension, Orthostatic / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics / Q000601:surgery*; D008297:Male; D010641:Phenotype; D011911:Rats, Gunn; D012709:Serum Albumin / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000201:enzymology / Q000378:metabolism*; D013997:Time Factors; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D015415:Biomarkers; D014453:Glucuronosyltransferase; D012709:Serum Albumin; D000099148:UGT1A1 Enzyme; C499946:Ugt1a1 protein, rat
keywords: Gunn rat; Hepatocyte; Liver stem/progenitor cells; Uridine diphosphate-glucuronosyltransferase 1A1; in vitro and in situ differentiation