Transplantation of encapsulated hepatocytes during acute liver failure improves survival without stimulating native liver regeneration

Article Article scientifique Article Transplantation of encapsulated hepatocytes during acute liver failure improves survival without stimulating native liver regeneration eng 2011-12-01 2011-12 author Sgroi Antonino Surgical Research Unit, Department of Surgery, University Hospital Geneva, Geneva, Switzerland. 507346 author Mai Gang 553550 author Morel Philippe 34882 author Baertschiger Reto Marc 548184 author Gonelle-Gispert Carmen 105800 author Serre Beinier Véronique 0000-0002-6016-1645 123229 Département de chirurgie (CHIRU) author Buehler Leo Hans 71923 1791-1803 10.3727/096368911X564976 21396154 0963-6897 http://journals.sagepub.com/doi/10.3727/096368911X564976 The aim of this study was to evaluate the effects of intraperitoneal transplantation of encapsulated human hepatocytes on liver metabolism and regeneration of mice with acute liver failure. Primary human hepatocytes were immortalized using lentiviral vectors coding for antiapoptotic genes and microencapsulated using alginate-polylysine polymers. In vitro, immortalized human hepatocytes showed low, but stable, synthetic and catabolitic functions over time, when compared to primary hepatocytes. In vivo, mice with acute liver failure and transplanted with encapsulated immortalized human hepatocytes had a significantly improved survival and biochemical profile, compared to mice transplanted with empty capsules. Serum levels of cytokines implicated in liver regeneration were lower in mice transplanted with hepatocytes compared to mice receiving empty capsules. This decrease was significant for IL-6 and HGF at 3 h. Measurement of liver regeneration showed no significant difference between mice transplanted with hepatocytes compared to control groups. Intraperitoneal transplantation of encapsulated immortalized hepatocytes significantly improved survival of mice with acute liver failure by providing metabolic support and without modifying liver regeneration. The lower levels of cytokines implicated in liver regeneration suggest that the metabolic support provided by the encapsulated hepatocytes reduced the inflammatory stress on the liver and herein decreased the regenerative trigger on residual hepatocytes. These data emphasize that metabolic function and regeneration of hepatocytes are two distinct aspects that need to be studied and approached separately during acute liver failure. Animals Aspartate Aminotransferases / blood Bilirubin / blood Capsules / chemistry Cell Proliferation Cell Survival Cells, Cultured Cytokines / blood Hepatocyte Growth Factor / blood Hepatocytes / cytology Hepatocytes / transplantation Humans Interleukin-6 / blood Liver / physiology Liver Failure, Acute / metabolism Liver Failure, Acute / mortality Liver Failure, Acute / therapy Liver Regeneration Male Mice Mice, Inbred C57BL Serum Albumin / metabolism Survival Rate Transplantation, Heterologous Dewey 617 Swiss National Science Foundation Impact of Hepatocyte transplantation on liver regeneration in fulminant hepatic failure 115048 CH Careers Swiss National Science Foundation Hepatocyte and adult mesenchymal stem cell transplantation for treatment of liver failure 109888 CH Projects 57 Département de chirurgie 222 false 902 Cancer du poumon et mésothéliome pleural malin 944 Cell transplantation 20 11-12 ee6f77db-0dcd-495a-b0c0-863598652986 Article (Published version) Public sgroi-et-al-2011-transplantation-of.pdf 352485 application/pdf 6af938e86c12c426289282650d7e4966d13d769ae56505da3d1f40c96f3f5aa3 openAccess Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Transplantation of encapsulated hepatocytes during acute liver failure improves survival without stimulating native liver regeneration	Cell transplantation	2011	31	125
Evaluation d'un programme de prévention dentaire dans une boulangerie-pâtisserie familiale		1996	295	276

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