Encapsulated xenogeneic hepatocytes remain functional after peritoneal implantation despite immunization of the host

Abstract

Background/Aims: Xenogeneic hepatocytes encapsulated in semipermeable membranes could be used in the future for the treatment of acute liver failure and congenital liver defects. However, host immune response could affect the viability and function of transplanted cells. The purpose of this study was to investigate the immunological consequences of intraperitoneal implantation of encapsulated xenogeneic hepatocytes and their effects. Methods: Recipient Lewis rats received 2×10 7 human hepatocytes encapsulated in semipermeable hydrogel-based hollow fibers, 2×10 7 free human hepatocytes or 2×10 7 encapsulated Lewis rat hepatocytes. The presence of human albumin in rat sera was assessed by Western blot and the presence of anti-human hepatocytes and anti-human albumin antibodies by ELISA. Results: Anti-hepatocyte antibodies were detected on the 7th day, and their level increased progressively on days 21 and 28 in rats grafted with encapsulated or free human hepatocytes. Anti-albumin antibodies were detected on day 7 and increased progressively in rats grafted with encapsulated human hepatocytes, but were not detected in the other groups. No immune complexes or complement components of donor origin were detected by immunofluorescence in the recipients' tissue. Despite immunization of the host, encapsulated xenogeneic hepatocytes survived and produced albumin, whereas free hepatocytes had been lysed. Conclusion: Transplantation of encapsulated xenogeneic hepatocytes resulted in immunization of the host with production of anti-hepatocyte and anti-albumin antibodies. However, hepatocytes could be efficiently protected by the membrane and remained viable and functional during the study.