title: Transplantation of human stem cell-derived hepatocytes in an animal model of acute liver failure.
abstract: BACKGROUND
  Hepatocyte cell transplantation can be life-saving in patients with acute liver failure (ALF); however, primary human hepatocyte transplantation is limited by the scarcity of donor hepatocytes. We investigated the effect of stem cell-derived, hepatocyte-like cells in an animal xenotransplant model of ALF.
  
  
  METHODS
  Intraperitoneal d-galactosamine was used to develop a lethal model of ALF in the rat. Human induced pluripotent stem cells (iPSC), human mesenchymal stem cells, and human iPSC combined with human endothelial cells (iPSC + EC) were differentiated into hepatocyte-like cells and transplanted into the spleens of athymic nude rats with ALF.
  
  
  RESULTS
  A reproducible lethal model of ALF was achieved with nearly 90% death within 3 days. Compared with negative controls, rats transplanted with stem cell-derived, hepatocyte-like cells were associated with increased survival. Human albumin was detected in the rat serum 3 days after transplantation in more than one-half the animals transplanted with hepatocyte-like cells. Only animals transplanted with iPSC + EC-derived hepatocytes had serum human albumin at 14 days posttransplant. Transplanted hepatocyte-like cells homed to the injured rat liver, whereas the ECs were only detected in the spleen.
  
  
  CONCLUSIONS
  Transplantation of stem cell-derived, hepatocyte-like cells improved survival with evidence of in vivo human albumin production. Combining ECs may prolong cell function after transplantation.
authors.affiliation: Department of Surgery, Virginia Commonwealth University, Richmond, VA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ramanathan
authors.affiliation: Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pettinato
authors.affiliation: Department of Surgery, Virginia Commonwealth University, Richmond, VA.
authors.forename: John T
authors.initials: JT
authors.lastname: Beeston
authors.affiliation: Department of Surgery, Mayo Clinic Jacksonville, Jacksonville, FL.
authors.forename: David D
authors.initials: DD
authors.lastname: Lee
authors.affiliation: Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Surgery, Virginia Commonwealth University, Richmond, VA.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Mangino
authors.affiliation: Transplant Institute, Beth Israel Deaconess Medical Center, Boston, MA. Electronic address: rafisher@bidmc.harvard.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fisher
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D017114:Liver Failure, Acute / Q000097:blood / Q000628:therapy*; D008297:Male; D059630:Mesenchymal Stem Cells; D051381:Rats; D011923:Rats, Nude; D014183:Transplantation, Heterologous / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D015415:Biomarkers