Prolonged Skin Graft Survival and Histocompatibility in Highly Inbred Miniature Swine

Pigs are potential organ donors for humans. Some proposed xenotransplant tolerance regimens require genetically identical cells from different animals (eg, juvenile bone marrow and mature organs or tissues). We therefore sought to develop a highly inbred line of miniature swine for this purpose. The aim of this study was to test histocompatibility in a new subline of highly inbred miniature swine.

Pigs from 2 generations with coefficient of inbreeding (COI) of 92% (n = 6) and 94% (n = 4) each received 2 split-thickness skin grafts (STSGs): an autograft and an allograft from the same generation. This was repeated in a group of 4 pigs from the generation with COI 92%. STSGs were followed for 28-35 d (COI 92%) or >380 d (COI 94%).

For the pigs with COI of 92%, 1 pig rejected the first allograft on day 9. All other pigs showed prolonged (>24 d) STSG survival. All subsequently rejected a second matched allograft in <14 d, indicating sensitization to minor histocompatibility antigens still segregating in the herd. For the pigs with COI of 94%, 1 pig rejected its allograft at day 9 while the other 3 accepted their allografts >386 d.

At COI of 92%, highly inbred swine experienced prolonged STSG survival, but persistent minor histocompatibility antigen disparities caused delayed skin graft rejection. Most pigs with COI of 94% accepted reciprocal skin grafts long-term without immunosuppression, indicating homozygosity of the skin graft donors for all relevant histocompatibility loci. Organ transplants within this new inbred line are expected to be accepted indefinitely without a requirement for exogenous immunosuppression, facilitating experiments requiring genetically identical cells from different animals.