Successful xenotransplantation with re-aggregated and encapsulated neonatal pig liver cells for treatment of mice with acute liver failure

• Published in: Xenotransplantation (Københaven) Vol. 22; no. 4; pp. 249 - 259
• Main Authors: Ham, Dong-Sik, Song, Min-Sang, Park, Heon-Seok, Rhee, Marie, Yang, Hae Kyung, Lee, Seung-Hwan, Kim, Ji-Won, Jung, Eun-Sun, Yoon, Kun-Ho
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.07.2015
• Subjects: Acetaminophen - toxicity; acute liver failure; Albumins - biosynthesis; Animals; Animals, Newborn; Cell Aggregation; Cell Survival; cell therapy; Cells, Cultured; Disease Models, Animal; Graft Survival; Hepatocytes - cytology; Hepatocytes - metabolism; Hepatocytes - transplantation; Humans; Liver Failure, Acute - chemically induced; Liver Failure, Acute - therapy; Male; Mice; Mice, Inbred C57BL; microencapsulation; neonatal pig; Spheroids, Cellular - transplantation; Sus scrofa; Swine; Swine, Miniature; Transplantation, Heterologous - methods; Urea - metabolism; xenotransplantation; xenotransplantation; acute liver failure; cell therapy; microencapsulation; neonatal pig
• ISSN: 0908-665X; 1399-3089; 1399-3089
• DOI: 10.1111/xen.12177

Background Hepatocyte transplantation is a promising therapy for acute liver failure. Cell therapy using xenogeneic sources has emerged as an alternative treatment for patients with organ failure due to the shortage of transplantable human organs. The purpose of this study was to improve the survival of mice with acute liver failure by transplanting encapsulated neonatal pig re‐aggregated liver cells (NPRLC). Methods Liver injury was induced in C57/BL6 male mice by the injection of 600 mg/kg of acetaminophen. Xenogeneic liver cells were isolated from a neonatal pig and processed via re‐aggregation and encapsulation to improve the efficiency of the xenogeneic liver cell transplantation. The neonatal pig liver showed abnormal lobule structure. Isolated cells were re‐aggregated and intraperitoneally transplanted into acute liver failure mice models. Results Re‐aggregated cells showed significantly enhanced viability and significantly greater synthesis of albumin and urea than cells cultured in monolayers. Further, we observed improved serum levels of ALT/AST, and the survival rate of mice with acute liver failure was improved by the intraperitoneal transplantation of encapsulated hepatocytes (48 000 equivalent (Eq) per mouse). Conclusions This study shows that using encapsulated NPRLCs improves the efficacy of xenogeneic liver cell transplantation for the treatment of mice with acute liver failure. Therefore, this may be a good strategy for bridge therapy for the treatment of acute liver failure in humans.