ArticleFrontiers in immunology2022
Xenotransplantation of Genetically Modified Neonatal Pig Islets Cures Diabetes in Baboons.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Review
- eVLP-Mediated Cas9 Delivery for Preventing IBMIR in Islet Transplantation.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Towards curing type 1 diabetes: Prospects and challenges of allogeneic or xenogeneic donor islet cell transplantation.World journal of transplantation · 2025Review
- Attitudes toward pig islet xenotransplantation for type 1 diabetes: a scoping review.Journal of endocrinological investigation · 2025Article
- Current status of pancreatic islet xenotransplantation.Clinical transplantation and research · 2025Review
- Allogeneic Islet Transplantation: Chronicle of a Death Foretold?Transplant international : official journal of the European Society for Organ Transplantation · 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
- Combined islet and kidney xenotransplantation for diabetic nephropathy: an update in ongoing research for a clinically relevant application of porcine islet transplantation.Frontiers in immunology · 2024Review
- What Genetic Modifications of Source Pigs Are Essential and Sufficient for Cell, Tissue, and Organ Xenotransplantation?Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Enhanced Insulin Production From Porcine Islets: More Insulin, Less Islets.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Ethical and legislative advances in xenotransplantation for clinical translation: focusing on cardiac, kidney and islet cell xenotransplantation.Frontiers in immunology · 2024Review
- A brief review of the current status of pig islet xenotransplantation.Frontiers in immunology · 2024Review
- Characterisation of transgenic pigs expressing a human T cell-depleting anti-CD2 monoclonal antibody.Xenotransplantation · 2023Article
- The Jewish Perspectives on Xenotransplantation.Rambam Maimonides medical journal · 2023Article
- Optimal temperature for the long-term culture of adult porcine islets for xenotransplantation.Frontiers in immunology · 2023Article
- Editorial: Xenotransplantation for the therapy of diabetes: A new look.Frontiers in endocrinology · 2023Article
- Article
- Progress in islet xenotransplantation: Immunologic barriers, advances in gene editing, and tolerance induction strategies for xenogeneic islets in pig-to-primate transplantation.Frontiers in transplantation · 2022Article
- Donor pigs for clinical islet xenotransplantation: Review and future directions.Cell transplantationReview
- Global Consultation for Clinical Xenotransplantation: International Xenotransplantation Association Consensus and Communiqué Update.XenotransplantationReview
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Xenotransplantation using porcine donors is rapidly approaching clinical applicability as an alternative therapy for treatment of many end-stage diseases including type 1 diabetes. Porcine neonatal islet cell clusters (NICC) have normalised blood sugar levels for relatively short periods in the preclinical diabetic rhesus model but have met with limited success in the stringent baboon model. Here we report that NICC from genetically modified (GM) pigs deleted for αGal and expressing the human complement regulators CD55 and CD59 can cure diabetes long-term in immunosuppressed baboons, with maximum graft survival exceeding 22 months. Five diabetic baboons were transplanted intraportally with 9,673 - 56,913 islet equivalents (IEQ) per kg recipient weight. Immunosuppression consisted of T cell depletion with an anti-CD2 mAb, tacrolimus for the first 4 months, and maintenance with belatacept and anti-CD154; no anti-inflammatory treatment or cytomegalovirus (CMV) prophylaxis/treatment was given. This protocol was well tolerated, with all recipients maintaining or gaining weight. Recipients became insulin-independent at a mean of 87 ± 43 days post-transplant and remained insulin-independent for 397 ± 174 days. Maximum graft survival was 675 days. Liver biopsies showed functional islets staining for all islet endocrine components, with no evidence of the inflammatory blood-mediated inflammatory reaction (IBMIR) and minimal leukocytic infiltration. The costimulation blockade-based immunosuppressive protocol prevented an anti-pig antibody response in all recipients. In conclusion, we demonstrate that genetic modification of the donor pig enables attenuation of early islet xenograft injury, and in conjunction with judicious immunosuppression provides excellent long-term function and graft survival in the diabetic baboon model.
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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.