Pig-to-Rabbit Islet Transplantation as an Immunologic Model of Pig-to-Human Islet Xenografts V.E. Papalois, J. Lee, W. McKane, N. Browning, A. Palmer, N. Hakim, T. Cairns, and D. Taube U NIMMUNIZED humans have natural antibody that binds to Gal1-3Gal expressed on pig red blood cells (RBC), mononuclear cells (PBMC), and vascular endothe- lial cells (VEC). 1 We have previously demonstrated that adult pig pancreata express Gal1-3Gal on the ductal cells (PDC) and intraislet capillaries (PIC) but not on the endocrine cells (PEC). 2 In addition, islets obtained from adult pig pancreata by collagenase digestion lose the Gal1- 3Gal expression found on the PIC. 2 Those studies demon- strated that the challenge of pig-to-human islet transplan- tation is different to that of vascularized solid organs. In the present study, we aimed to define a small animal combina- tion that would be humorally indistinct from pig-to-human, to allow a full description of the sequence of histologic and immunologic events following islet xenotransplantation. MATERIALS AND METHODS We investigated the binding of natural anti-pig antibody to RBC, PBMC, VEC, PDC, PIC, PEC, and purified islets (PI) in humans and in three selected species: mouse (C57BL/6), rat (Sprague Dawley), and rabbit (Half Lop). Antibody binding was assessed by hemagglutination (RBC), flow cytometry (PBMC), and immuno- histochemistry (VEC, PDC, PIC, PI). RESULTS The results are presented in Table 1. Only the pig-to rabbit combination provided the same antibody profile as pig-to- human. Rat and mouse models have been previously used as recipients in pig islet xenotransplantation, but our results show that they are not adequate pig-to-human immunologic surrogates. DISCUSSION Methods for induction of diabetes in rabbits are well established 3 and the pig-to-rabbit islet xenotransplantation model allows studies of graft function as well as of histo- logic and immunologic events. We have started a program of islet xenotransplantation in rabbits by intrahepatic injec- tion of unpurified pig islets isolated by using the Ricordi semiautomated method. 4 Provisional data indicate that residual nonendocrine tissue causes necrosis and a mixed infiltrate. Insulin staining indicates that isolated islets sur- vive at the time of sacrifice (5 to 6 days) without provoking a local infiltrate. REFERENCES 1. Platt JL, Parker W, Linn SS, et al: In Cooper DKC, Kemp E, Platt JL, et al (eds): Xenotransplantation. Berlin: Springer-Verlag; 1997, p 16 2. Papalois VE, Romagnoli J, Lee J, et al: Transplant Proc 30:656, 1998 3. Mumtaz FH, Sullivan ME, Thompson CS, et al: J Urol 162:558, 1999 4. Ricordi C, Socci C, Davalli AM, et al: Surgery 107:688, 1990 From Brent Laboratory, St Mary’s Hospital, London, United Kingdom. Address reprint requests to V.E. Papalois, Brent Laboratory, St Mary’s Hospital, Praed Street, London W2 1NY, United Kingdom. Table 1. Results of Binding () or no Binding () of Mouse, Rat, Rabbit, and Human Antibody to Different Pig Cell Types Species RBC PBMC VEC PDC PIC PEC PI Mouse - - + + - + + Rat - - + + - - - Rabbit + + + + + - - Human + + + + + - - 0041-1345/00/$–see front matter © 2000 by Elsevier Science Inc. PII S0041-1345(00)01128-3 655 Avenue of the Americas, New York, NY 10010 1070 Transplantation Proceedings, 32, 1070 (2000)