Long‐term survival of pig‐to‐mouse Islet xenografts

Abstract

Abstract: Several laboratories are currently able to prepare large amounts of purified porcine islets of proven in vitro viability. The long‐term in vivo function of pig islet xenografts has been evaluated in both “nonimmunocompetent” animals (i.e., the nude mouse) and “immunocompetent” animals. In the nude mouse, documentation has been provided for pig islet function for up to 4 months, even though the issue of how quickly porcine islet xenografts restore normal blood glucose in this animal model is still controversial. Interestingly, pig islet xenografts drive glucose metabolism to maintain plasma glucose concentrations at the donor species levels. Porcine islets have been also transplanted into varying “immunocompetent” animals species. Long‐term pig islet xenograft survival in rats and larger animals has been achieved by transplanting islets immunoisolated by either macro‐ or microencapsulation techniques. In the pig‐to‐mouse experimental model, freshly prepared, nonimmunoisolated islets survived long‐term (for up to 50–60 days) when anti‐CD4 antibody treatment was given temporarily posttransplant. Neither the addition of either mouse and/or pig anti‐lymphocyte serum, nor the use of 1 week, low‐temperature cultured, or cryopreserved islets did further prolong the survival. When 2 to 3 week cultured islets were transplanted into anti‐CD4 antibody treated mice, function of the xenografts was observed at 100 days posttransplant in 75% of the animals. Thus, long‐term survival of pig‐to‐mouse islet xenografts in both nonimmunocompetent and immunocompetent animals is achievable. Although further studies are needed to fully understand the hormonal and metabolic effects of the islet xenografts, as well as to extend some of the results obtained in mice to larger animal models, the in vivo data available so far support the use of pig islets for potential use in human xenotransplantation studies.