Prolonged Survival of Porcine Hepatocytes in Cynomolgus Monkeys

Hideo Nagata, Ryuta Nishitai, Chiyoe Shirota, Jia Lin Zhang, Cody A. Koch, Jin Cai, Michel Awwad, Henk Jan Schuurman, Uwe Christians, Michio Abe, Janina Baranowska-Kortylewicz, Jeffrey L. Platt, Ira J. Fox

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Background & Aims: Management of patients with liver failure can be a significant medical challenge, and transplantation of the liver is the only definitive therapy. Whole liver allotransplantation is limited by a shortage of human donors and the risks of the surgery in those most ill. Transplants consisting of xenogeneic hepatocytes might overcome these problems, and work in rodents indicates that such transplants can correct some metabolic deficiencies and can prevent the complications and mortality associated with hepatic failure. As a prelude to clinical application, we tested the feasibility of hepatocyte xenotransplantation in nonhuman primates. Methods: One to 2 billion hepatocytes from outbred swine were transplanted into the spleens of cynomolgus monkeys using conventional immunosuppression to control rejection. Duration of graft function was determined based on assay for porcine albumin. Results: Following a single infusion, xenogeneic hepatocytes functioned for more than 80 days and, following re-transplantation, for more than 253 days. Engraftment in the spleen was confirmed 40 days after transplantation by asialoglycoprotein receptor-directed nuclear scanning. The humoral immune response to the transplanted porcine cells had no discernible impact on the survival of the grafts. Conclusions: Xenotransplantation of hepatocytes should be explored as a readily available, minimally invasive form of therapy for hepatic failure.

Original languageEnglish (US)
Pages (from-to)321-329
Number of pages9
JournalGastroenterology
Volume132
Issue number1
DOIs
StatePublished - Jan 2007

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Nagata, H., Nishitai, R., Shirota, C., Zhang, J. L., Koch, C. A., Cai, J., Awwad, M., Schuurman, H. J., Christians, U., Abe, M., Baranowska-Kortylewicz, J., Platt, J. L., & Fox, I. J. (2007). Prolonged Survival of Porcine Hepatocytes in Cynomolgus Monkeys. Gastroenterology, 132(1), 321-329. https://doi.org/10.1053/j.gastro.2006.10.013