Abstract
INTRODUCTION: Cell transplantation is an alternative to liver transplantation, which is hampered by short survival time and immunorejection. The goal of this study was to evaluate the therapeutic potential of hepatocytes coencapsulated with adipose-derived stem cells (ADSCs) in treating acute-on-chronic liver failure (ACLF). METHODS: Rat hepatocytes and ADSCs were isolated, and coencapsulated by alginate-poly-L-lysine-alginate microencapsulation. The morphological and functional changes of heterotypic interactions were characterized. ACLF in rats was induced by D-galactosamine administration following CCl4-induced cirrhosis. These rats were subjected to intraperitoneal transplantation of 5 × 107 coencapsulated hepatocytes with ADSCs, 5 × 107 encapsulated hepatocytes alone, or empty vehicles after 24 h, respectively. The survival rate and liver functions were assessed. RESULTS: Hepatocyte performance levels such as albumin secretion and urea synthesis induction were all significantly enhanced in the coencapsulation group compared with the homo-encapsulated hepatocytes group (p<0.05). The results of cell cycle analysis showed that larger populations of hepatocytes with ADSC treatment were accumulated in the G2-S phase, and there were fewer in the G0-G1 phase compared to encapsulation of hepatocytes alone. Intraperitoneal transplantation of coencapsulated hepatocytes with ADSCs not only increased the survival rate, but also improved liver functions in a rat model of ACLF. CONCLUSIONS: Transplantation of coencapsulated hepatocytes and ADSCs might be a promising strategy for cell-based therapy of acute liver diseases.