Transplantation of Encapsulated Hepatocytes during Acute Liver Failure Improves Survival without Stimulating Native Liver Regeneration
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 microe...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
SAGE Publishing
2011-12-01
|
Series: | Cell Transplantation |
Online Access: | https://doi.org/10.3727/096368911X564976 |
id |
doaj-4732a0dc08544650a784c32cbd620217 |
---|---|
record_format |
Article |
spelling |
doaj-4732a0dc08544650a784c32cbd6202172020-11-25T03:20:54ZengSAGE PublishingCell Transplantation0963-68971555-38922011-12-012010.3727/096368911X564976Transplantation of Encapsulated Hepatocytes during Acute Liver Failure Improves Survival without Stimulating Native Liver RegenerationAntonino Sgroi0Gang Mai1Philippe Morel2Reto M. Baertschiger3Carmen Gonelle-Gispert4Véronique Serre-Beinier5Leo H. Buhler M.D.6Department of General Surgery, West China Hospital, Sichuan University, Sichuan Province, ChinaDepartment of General Surgery, West China Hospital, Sichuan University, Sichuan Province, ChinaSurgical Research Unit, Department of Surgery, University Hospital Geneva, Geneva, SwitzerlandSurgical Research Unit, Department of Surgery, University Hospital Geneva, Geneva, SwitzerlandSurgical Research Unit, Department of Surgery, University Hospital Geneva, Geneva, SwitzerlandSurgical Research Unit, Department of Surgery, University Hospital Geneva, Geneva, SwitzerlandSurgical Research Unit, Department of Surgery, University Hospital Geneva, Geneva, SwitzerlandThe 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.https://doi.org/10.3727/096368911X564976 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Antonino Sgroi Gang Mai Philippe Morel Reto M. Baertschiger Carmen Gonelle-Gispert Véronique Serre-Beinier Leo H. Buhler M.D. |
spellingShingle |
Antonino Sgroi Gang Mai Philippe Morel Reto M. Baertschiger Carmen Gonelle-Gispert Véronique Serre-Beinier Leo H. Buhler M.D. Transplantation of Encapsulated Hepatocytes during Acute Liver Failure Improves Survival without Stimulating Native Liver Regeneration Cell Transplantation |
author_facet |
Antonino Sgroi Gang Mai Philippe Morel Reto M. Baertschiger Carmen Gonelle-Gispert Véronique Serre-Beinier Leo H. Buhler M.D. |
author_sort |
Antonino Sgroi |
title |
Transplantation of Encapsulated Hepatocytes during Acute Liver Failure Improves Survival without Stimulating Native Liver Regeneration |
title_short |
Transplantation of Encapsulated Hepatocytes during Acute Liver Failure Improves Survival without Stimulating Native Liver Regeneration |
title_full |
Transplantation of Encapsulated Hepatocytes during Acute Liver Failure Improves Survival without Stimulating Native Liver Regeneration |
title_fullStr |
Transplantation of Encapsulated Hepatocytes during Acute Liver Failure Improves Survival without Stimulating Native Liver Regeneration |
title_full_unstemmed |
Transplantation of Encapsulated Hepatocytes during Acute Liver Failure Improves Survival without Stimulating Native Liver Regeneration |
title_sort |
transplantation of encapsulated hepatocytes during acute liver failure improves survival without stimulating native liver regeneration |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2011-12-01 |
description |
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. |
url |
https://doi.org/10.3727/096368911X564976 |
work_keys_str_mv |
AT antoninosgroi transplantationofencapsulatedhepatocytesduringacuteliverfailureimprovessurvivalwithoutstimulatingnativeliverregeneration AT gangmai transplantationofencapsulatedhepatocytesduringacuteliverfailureimprovessurvivalwithoutstimulatingnativeliverregeneration AT philippemorel transplantationofencapsulatedhepatocytesduringacuteliverfailureimprovessurvivalwithoutstimulatingnativeliverregeneration AT retombaertschiger transplantationofencapsulatedhepatocytesduringacuteliverfailureimprovessurvivalwithoutstimulatingnativeliverregeneration AT carmengonellegispert transplantationofencapsulatedhepatocytesduringacuteliverfailureimprovessurvivalwithoutstimulatingnativeliverregeneration AT veroniqueserrebeinier transplantationofencapsulatedhepatocytesduringacuteliverfailureimprovessurvivalwithoutstimulatingnativeliverregeneration AT leohbuhlermd transplantationofencapsulatedhepatocytesduringacuteliverfailureimprovessurvivalwithoutstimulatingnativeliverregeneration |
_version_ |
1724615806551064576 |