Co-transplantation of encapsulated HepG2 and rat Sertoli cells improves outcome in a thioacetamide induced rat model of acute hepatic failure.

Hepatocyte transplantation offers therapeutic opportunities in liver disease. Xenogeneic hepatocytes are a potential resource, but rejection presents a major problem. We combined cell encapsulation with modulation by local generation of an immunosuppressant by co-encapsulating Sertoli cells with HepG2 cells. We assessed in vitro rat leukocyte proliferative responses and HepG2 cell survival after intraperitoneal injection in rats. Empty beads, and beads containing HepG2 cells or HepG2/Sertoli cells were injected intra-peritoneally into rats and survival of implanted cells followed over 4 weeks; in some animals acute hepatic failure (AHF) using thioacetamide (TAA) was also induced. The marked proliferative response of rat leukocytes to HepG2 cells and HepG2-containing beads was reduced by Sertoli cell-conditioned medium and HepG2/Sertoli encapsulates. After intra-peritoneal transplantation, Sertoli cells co-encapsulation protected the HepG2 cells in normal and AHF animals. Combined encapsulation and locally generated immuno-suppression may be a valuable strategy in hepatocyte transplantation.

Alginate-encapsulated human hepatoblastoma cells in an extracorporeal perfusion system improve some systemic parameters of liver failure in a xenogeneic model.

Previous studies have demonstrated that alginate encapsulation of proliferating hepatocyte-derived cell lines (e.g., HepG2 cells) enhances the expression of differentiated hepatocyte function compared with conventional monolayer culture. Furthermore, such capsules have the advantage of cryopreservability, and can be readily manipulated, e.g., for the charging of extracorporeal devices. We utilize a rabbit model of acute liver failure caused by acetaminophen administration to rabbits pretreated to enhance cytochrome p450 enzyme activity, and demonstrate that encapsulated HepG2 cells, in an extracorporeal chamber, perfused by rabbit plasma separated on-line at a rate of 2-5 mL/min, and perfused over cells at 40-60 mL/min, improve systemic parameters of liver failure (diastolic blood pressure and transjugular venous oxygen saturation). Such encapsulated cells have the potential to be developed for extracorporeal liver support systems for acute liver failure.