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We found that an induction immunotherapy regimen consisting of rabbit anti-thymocyte globulin (Thymoglobulin) and the monoclonal antibody to CD20 rituximab (Rituxan) promoted long-term islet allograft survival in cynomolgus macaques maintained on rapamycin monotherapy. B lymphocyte reconstitution after rituximab-mediated depletion was characterized by a preponderance of immature and transitional cells, whose persistence was associated with long-term islet allograft survival. Development of donor-specific alloantibodies was abrogated only in the setting of continued rapamycin monotherapy.
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http://dx.doi.org/10.1038/nm1673 | DOI Listing |
Front Biosci (Landmark Ed)
August 2025
School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia.
Transcription factors are significant regulators of gene expression in most biological processes related to diabetes, including beta cell (β-cell) development, insulin secretion and glucose metabolism. Dysregulation of transcription factor expression or abundance has been closely associated with the pathogenesis of type 1 and type 2 diabetes, including pancreatic and duodenal homeobox 1 (), neurogenic differentiation 1 (), and forkhead box protein O1 (). Gene expression is regulated at the transcriptional level by transcription factor binding, epigenetically by DNA methylation and chromatin remodelling, and post-transcriptional mechanisms, including alternative splicing and microRNA (miRNA).
View Article and Find Full Text PDFDiabetes Metab J
September 2025
Institute of Medical & Public Health Research, Ilia State University, Tbilisi, Georgia.
Background: The long-term clinical efficacy of intraportal islet transplantation is hampered by islet loss due to inflammation, oxidative stress, and insufficient vascularization. This study explores the venous sac as an alternative implantation site for islet transplantation in large animal models.
Methods: An immunosuppressed, diabetic cynomolgus monkey received allogeneic islet implants in its mesenteric venous sac, with metabolic assessments over 112 days.
Front Immunol
September 2025
Chemical and Biological Engineering, Koc University, Istanbul, Türkiye.
Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic beta cells, resulting in lifelong insulin therapy that falls short of a true cure. Beta cell replacement therapies hold immense potential to restore natural insulin production, but they face significant hurdles such as immune rejection, limited donor availability, and long-term graft survival. In this review, we explore cutting-edge advances in genetic engineering, biomaterials, and machine learning approaches designed to overcome these barriers and enhance the clinical applicability of beta cell therapies.
View Article and Find Full Text PDFJ Clin Med
August 2025
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
Type 1 diabetes mellitus (T1DM) is an autoimmune condition in which pancreatic β-cells are selectively destroyed, predominantly by autoreactive T lymphocytes. Despite decades of research, the achievement of durable immune tolerance remains elusive. This review presents a historically grounded and forward-looking perspective on the evolution of immunotherapy in T1DM, from early immunosuppressive interventions to advanced precision-based cellular approaches.
View Article and Find Full Text PDFFront Transplant
August 2025
Department of Biomedical Engineering, Northwestern University, Chicago, IL, United States.
Introduction: Islet transplantation offers a potential curative treatment for patients with type 1 diabetes (T1D). To make this therapy widely available, a stable supply chain of human islets is essential. Developing techniques like cryopreservation and culture for long-term islet storage, or islet banking, with minimal functional loss would strengthen this supply chain.
View Article and Find Full Text PDF