biostudies-literatureGraham MLNational Institute of Allergy and Infectious DiseasesNIAID NIH HHSJuvenile Diabetes Research Foundation United Kingdom745-760https://www.ebi.ac.uk/biostudies/studies/S-EPMC9832996biostudies-literatureUnknown22(3)A safe, efficacious, and clinically applicable immunosuppressive regimen is necessary for islet xenotransplantation to become a viable treatment option for diabetes. We performed intraportal transplants of wild-type adult porcine islets in 25 streptozotocin-diabetic cynomolgus monkeys. Islet engraftment was good in 21, partial in 3, and poor in 1 recipient. Median xenograft survival was 25 days with rapamycin and CTLA4Ig immunosuppression. Adding basiliximab induction and maintenance tacrolimus to the base regimen significantly extended median graft survival to 147 days (p < .0001), with three animals maintaining insulin-free xenograft survival for 265, 282, and 288 days. We demonstrate that this regimen suppresses non-Gal anti-pig antibody responses, circulating effector memory T cell expAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant SurgeonsClinically available immunosuppression averts rejection but not systemic inflammation after porcine islet xenotransplant in cynomolgus macaques.PMC98329967U19AI06715121‐2006‐881U19 AI067151Anazawa TRamachandran SSingh AFlanagan EBAppakalai BNPapas KKSpizzo TBansal-Pakala PBurlak CAzimzadeh AMartins KMueller KRHancock WWMoore MEGSchuurman HJHering BJMurtaugh MPGraham MLO'Brien TDfalseClinically available immunosuppression averts rejection but not systemic inflammation after porcine islet xenotransplant in cynomolgus macaques.A safe, efficacious, and clinically applicable immunosuppressive regimen is necessary for islet xenotransplantation to become a viable treatment option for diabetes. We performed intraportal transplants of wild-type adult porcine islets in 25 streptozotocin-diabetic cynomolgus monkeys. Islet engraftment was good in 21, partial in 3, and poor in 1 recipient. Median xenograft survival was 25 days with rapamycin and CTLA4Ig immunosuppression. Adding basiliximab induction and maintenance tacrolimus to the base regimen significantly extended median graft survival to 147 days (p < .0001), with three animals maintaining insulin-free xenograft survival for 265, 282, and 288 days. We demonstrate that this regimen suppresses non-Gal anti-pig antibody responses, circulating effector memory T cell exp2022-01-01T00:00:00Z2022 Mar2025-04-04T21:43:40.927Z2025-04-04T21:43:40.927ZS-EPMC98329963470434510.1111/ajt.16876