title: Successful xenotransplantation with re-aggregated and encapsulated neonatal pig liver cells for treatment of mice with acute liver failure.
abstract: BACKGROUND
  Hepatocyte transplantation is a promising therapy for acute liver failure. Cell therapy using xenogeneic sources has emerged as an alternative treatment for patients with organ failure due to the shortage of transplantable human organs. The purpose of this study was to improve the survival of mice with acute liver failure by transplanting encapsulated neonatal pig re-aggregated liver cells (NPRLC).
  
  
  METHODS
  Liver injury was induced in C57/BL6 male mice by the injection of 600 mg/kg of acetaminophen. Xenogeneic liver cells were isolated from a neonatal pig and processed via re-aggregation and encapsulation to improve the efficiency of the xenogeneic liver cell transplantation. The neonatal pig liver showed abnormal lobule structure. Isolated cells were re-aggregated and intraperitoneally transplanted into acute liver failure mice models.
  
  
  RESULTS
  Re-aggregated cells showed significantly enhanced viability and significantly greater synthesis of albumin and urea than cells cultured in monolayers. Further, we observed improved serum levels of ALT/AST, and the survival rate of mice with acute liver failure was improved by the intraperitoneal transplantation of encapsulated hepatocytes (48,000 equivalent (Eq) per mouse).
  
  
  CONCLUSIONS
  This study shows that using encapsulated NPRLCs improves the efficacy of xenogeneic liver cell transplantation for the treatment of mice with acute liver failure. Therefore, this may be a good strategy for bridge therapy for the treatment of acute liver failure in humans.
authors.affiliation: Department of Endocrinology & Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Dong-Sik
authors.initials: DS
authors.lastname: Ham
authors.affiliation: Department of Endocrinology & Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Min-Sang
authors.initials: MS
authors.lastname: Song
authors.affiliation: Department of Endocrinology & Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Heon-Seok
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Endocrinology & Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Marie
authors.initials: M
authors.lastname: Rhee
authors.affiliation: Department of Endocrinology & Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hae Kyung
authors.initials: HK
authors.lastname: Yang
authors.affiliation: Department of Endocrinology & Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Endocrinology & Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, Seoul, Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Hospital Pathology, The Catholic University of Korea, Seoul, Korea.
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Jung
authors.affiliation: Department of Endocrinology & Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, Seoul, Korea.
authors.forename: Kun-Ho
authors.initials: KH
authors.lastname: Yoon
mesh_terms: D000082:Acetaminophen / Q000633:toxicity; D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn; D002449:Cell Aggregation; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006085:Graft Survival; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018874:Spheroids, Cellular / Q000637:transplantation; D034421:Sus scrofa; D013552:Swine; D013556:Swine, Miniature; D014183:Transplantation, Heterologous / Q000379:methods*; D014508:Urea / Q000378:metabolism
chemical_list: D000418:Albumins; D000082:Acetaminophen; D014508:Urea
keywords: acute liver failure; cell therapy; microencapsulation; neonatal pig; xenotransplantation