ArticleDiabetes2012
Xenografted islet cell clusters from INSLEA29Y transgenic pigs rescue diabetes and prevent immune rejection in humanized mice.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 130 citations in OpenAlex.
- T cell-mediated immune responses in xenotransplantation: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Engineering hypoimmune stem cell-derived beta cells.Stem cell research & therapy · 2025Review
- Current status of xenotransplantation from an immunobiological standpoint.Clinical transplantation and research · 2025Review
- Cytotoxic Responses Mediated by NK Cells and Cytotoxic T Lymphocytes in Xenotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Immune-evasive beta cells in type 1 diabetes: innovations in genetic engineering, biomaterials, and computational modeling.Frontiers in immunology · 2025Review
- Immunoprotection Strategies in β-Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Characterisation of transgenic pigs expressing a human T cell-depleting anti-CD2 monoclonal antibody.Xenotransplantation · 2023Article
- Milestones on the path to clinical pig organ xenotransplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Review
- Cardiac xenotransplantation: from concept to clinic.Cardiovascular research · 2023Review
- Progress in xenotransplantation: overcoming immune barriers.Nature reviews. Nephrology · 2022Review
- Far-red light-activated human islet-like designer cells enable sustained fine-tuned secretion of insulin for glucose control.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Formation of Re-Aggregated Neonatal Porcine Islet Clusters ImprovesTransplant international : official journal of the European Society for Organ Transplantation · 2022Article
- Xenotransplantation of Genetically Modified Neonatal Pig Islets Cures Diabetes in Baboons.Frontiers in immunology · 2022Article
- Sequential in vivo labeling of insulin secretory granule pools inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- In Vivo Differentiation of Stem Cell-derived Human Pancreatic Progenitors to Treat Type 1 Diabetes.Stem cell reviews and reports · 2020Review
- Diabetes Mellitus Is a Chronic Disease that Can Benefit from Therapy with Induced Pluripotent Stem Cells.International journal of molecular sciences · 2020Review
- A decade of experience with genetically tailored pig models for diabetes and metabolic research.Animal reproduction · 2020Review
- Rejection of xenogeneic porcine islets in humanized mice is characterized by graft-infiltrating Th17 cells and activated B cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Article
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 IL2Rγ(null) 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.
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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.