Improved Xenogenic Hepatocyte Implantation into Nude Mouse Liver Parenchyma with Acute Liver Failure when Followed by Repeated Anti-Fas Antibody (Jo2) Treatment

Cell Transplantation

Article

Isabelle Vidal¹  Lysiane Richert²  Bruno Heyd³  Huseyin Firat⁴  Arnaud Gandillet⁵  Eliane Alexandre⁵  Daniel Jaeck⁶  Philippe Bachellier⁶  Nadège Blanchard⁷  Frank Staedtler⁸  Martin Schumacher⁸  Marie-Pierre Chenard-Neu⁹ 

[1] EA 3921, IFR 133, Faculté de Médecine et de Pharmacie, Besançon, France;Laboratoire de Chirurgie Expérimentale, Fondation Transplantation, Strasbourg, France;EA 3921, IFR 133, Faculté de Médecine et de Pharmacie, Besançon, France;Laboratoire de Chirurgie Expérimentale, Fondation Transplantation, Strasbourg, France;KaLy-Cell, Témis Innovation, Besançon, France;EA 3921, IFR 133, Faculté de Médecine et de Pharmacie, Besançon, France;Service de Chirurgie Digestive et Vasculaire, Hôpital Jean Minjoz, Besançon, France;Firalis SAS, Huningue, France;Laboratoire de Chirurgie Expérimentale, Fondation Transplantation, Strasbourg, France;Laboratoire de Chirurgie Expérimentale, Fondation Transplantation, Strasbourg, France;Centre de Chirurgie Viscérale et de Transplantation, Hôpital de Hautepierre, Strasbourg, France;Laboratoire de Chirurgie Expérimentale, Fondation Transplantation, Strasbourg, France;KaLy-Cell, Témis Innovation, Besançon, France;Novartis Pharma AG, Biomarker Development, Basel, Switzerland;Service d'Anatomo-Pathologie, Hôpital de Hautepierre, Strasbourg, France;

关键词: Nude mice;    Anti-Fas antibody treatment;    Xenogeneic hepatocyte engraftment;    Circadian genes;    p21;   

DOI  :  10.3727/096368908785096051

 received in 2006-01-02, accepted in 2007-10-03,  发布年份 2008

来源: Sage Journals

【 摘 要 】

Hepatocyte transplantation is a promising therapy for acute liver failure in humans. Recently, we succeeded in inducing various acute and chronic liver failures in nude mice. Engraftment of transplanted xenogeneic rat hepatocytes, visualized in the host liver by anti-MHC class I immunohistochemistry, revealed that liver repopulation was limited, and equivalent in nude mice with and without acute liver failure. In the present study, acute liver failure was induced in nude mice by a single injection of sublethal anti-Fas antibody Jo2, followed 24 h later by rat hepatocyte transplantation and than by a weekly repeated injection of Jo2. Rat hepatocyte engraftment into the recipient liver parenchyma 3 weeks following hepatocyte transplantation was about sevenfold increased when nude mice were subsequently subjected to weekly repeated Jo2 injection. Genomic analysis of these mice showed an overall transcriptome profile of upregulation of cellular cycle blocking transcripts, activation of liver injury inducing IFN-γ/STAT1 pathway, and circadian transcript signature of antiproliferative cell status compared to mice submitted to hepatocyte transplantation only. The findings of the present study suggest that the induction of cell proliferation blockade in recipient livers could promote sufficient engraftment of transplanted hepatocytes to allow transient or definitive treatment of liver failure in humans.

【 授权许可】

Unknown   
© 2008 Cognizant Comm. Corp.