PT  - JOURNAL ARTICLE
AU  - Klymiuk, Nikolai
AU  - van Buerck, Lelia
AU  - Bähr, Andrea
AU  - Offers, Monika
AU  - Kessler, Barbara
AU  - Wuensch, Annegret
AU  - Kurome, Mayuko
AU  - Thormann, Michael
AU  - Lochner, Katharina
AU  - Nagashima, Hiroshi
AU  - Herbach, Nadja
AU  - Wanke, Rüdiger
AU  - Seissler, Jochen
AU  - Wolf, Eckhard
TI  - Xenografted Islet Cell Clusters From <em>INS</em>LEA29Y Transgenic Pigs Rescue Diabetes and Prevent Immune Rejection in Humanized Mice
AID  - 10.2337/db11-1325
DP  - 2012 Jun 01
TA  - Diabetes
PG  - 1527--1532
VI  - 61
IP  - 6
4099  - http://diabetes.diabetesjournals.org/content/61/6/1527.short
4100  - http://diabetes.diabetesjournals.org/content/61/6/1527.full
SO  - Diabetes2012 Jun 01; 61
AB  - Islet transplantation is a potential treatment for type 1 diabetes, but the shortage of donor organs limits its routine application. As potential donor animals, we generated transgenic pigs expressing LEA29Y, a high-affinity variant of the T-cell costimulation inhibitor CTLA-4Ig, under the control of the porcine insulin gene promoter. Neonatal islet cell clusters (ICCs) from INSLEA29Y transgenic (LEA-tg) pigs and wild-type controls were transplanted into streptozotocin-induced hyperglycemic NOD-scid IL2Rγnull mice. Cloned LEA-tg pigs are healthy and exhibit a strong β-cell–specific transgene expression. LEA-tg ICCs displayed the same potential to normalize glucose homeostasis as wild-type ICCs after transplantation. After adoptive transfer of human peripheral blood mononuclear cells, transplanted LEA-tg ICCs were completely protected from rejection, whereas reoccurrence of hyperglycemia was observed in 80% of mice transplanted with wild-type ICCs. In the current study, we provide the first proof-of-principle report on transgenic pigs with β-cell–specific expression of LEA29Y and their successful application as donors in a xenotransplantation model. This approach may represent a major step toward the development of a novel strategy for pig-to-human islet transplantation without side effects of systemic immunosuppression.