ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2022
Clinically available immunosuppression averts rejection but not systemic inflammation after porcine islet xenotransplant in cynomolgus macaques.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Trajectory-based weight modeling distinguishes pathologic weight loss and predicts adverse events in nonhuman primate allogeneic kidney transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Genetically engineered porcine liver: a new era in transplantation.International journal of surgery (London, England) · 2026Article
- The Japanese Macaque as a Diabetes Recipient Animal Model for Porcine Islet Xenotransplantation.MedComm · 2026Article
- Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead.Nature reviews. Endocrinology · 2025Review
- Contributions of Europeans to Xenotransplantation Research: 2. Pig Islet and Cell Xenotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Ischemia Reperfusion Injury Induced Systemic Inflammatory Response Following Interspecies Liver Transplantation.Hepatic medicine : evidence and research · 2025Article
- Double transgenic neonatal porcine islets as an alternative source for beta cell replacement therapy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A bioengineered artificial interstitium supports long-term islet xenograft survival in nonhuman primates without immunosuppression.Science advances · 2024Article
- Enhanced Insulin Production From Porcine Islets: More Insulin, Less Islets.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Pig-to-Human xenotransplantation: Moving toward organ customization.Precision clinical medicine · 2023Article
- Progress in xenotransplantation: overcoming immune barriers.Nature reviews. Nephrology · 2022Review
- Cellular Immune Responses in Islet Xenograft Rejection.Frontiers in immunology · 2022Review
- Xenotransplantation of Genetically Modified Neonatal Pig Islets Cures Diabetes in Baboons.Frontiers in immunology · 2022Article
- Neutrophil to Lymphocyte Ratio (NLR) as an Easily Accessible Parameter for Monitoring Tacrolimus Overdose after Heart Transplantation-Experimental Study.Diagnostics (Basel, Switzerland) · 2021Article
- Distinct Pro-Inflammatory Species-Specific Transcriptional Changes in Human T Cells Following Pig Xenogeneic Stimulation.XenotransplantationArticle
- Cellular Dynamics of Transgenic Porcine Endothelial Cells to Inflammatory Stimuli in Xenotransplantation Settings.XenotransplantationArticle
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
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 expansion, effector function, and infiltration of the graft. However, a chronic systemic inflammatory state manifested in the majority of recipients with long-term graft survival indicated by increased neutrophil to lymphocyte ratio, IL-6, MCP-1, CD40, and CRP expression. This suggests that this immunosuppression regimen fails to regulate innate immunity and resulting inflammation is significantly associated with increased incidence and severity of adverse events making this regimen unacceptable for translation. Additional studies are needed to optimize a maintenance regimen for regulating the innate inflammatory response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.