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Type 1 diabetes mellitus is characterized by absolute insulin deficiency, which requires life-long insulin replacement. Exogenous multiple-daily insulin injections are most commonly prescribed for patients with type 1 diabetes mellitus. However, exogenous insulin supply often fails to cope with real-time changing life-log variables, such as activity, diet and stress, which results in recurrent hypo- and hyperglycemia in patients with type 1 diabetes mellitus. Islet transplantation is an ideal method to treat patients with type 1 diabetes mellitus, as it can restore the endogenous capacity of glucose-stimulated insulin secretion. However, due to donor scarcity and technical barriers, only a limited number of islet transplantations have been carried out in Asia, including South Korea. Since 2013, our center has carried out two allogenic islet transplantations, with one case leading to near total insulin independence after one-to-one islet transplantation. Although the other patient failed to restore endogenous insulin production, there was a remarkable improvement in hypoglycemia. We speculate that islet transplantation remains an important and ideal treatment option for patients with type 1 diabetes mellitus who suffer from recurrent severe hypoglycemia.

Islet transplantation is a promising therapy for diabetes treatment. However, the molecular underpinnings governing the immune response, particularly T-cell dynamics in syngeneic and allogeneic transplant settings, remain poorly understood. Understanding these T cell dynamics is crucial for enhancing graft acceptance and managing diabetes treatment more effectively. This study aimed to elucidate the molecular mechanisms, gene expression differences, biological pathway alterations, and intercellular communication patterns among T-cell subpopulations after syngeneic and allogeneic islet transplantation. Using single-cell RNA sequencing, we analyzed cellular heterogeneity and gene expression profiles using the Seurat package for quality control and dimensionality reduction through t-SNE. Differentially expressed genes (DEGs) were analyzed among different T cell subtypes. GSEA was conducted utilizing the HALLMARK gene sets from MSigDB, while CellChat was used to infer and visualize cell-cell communication networks. Our findings revealed genetic variations within T-cell subpopulations between syngeneic and allogeneic islet transplants. We identified significant DEGs across these conditions, highlighting molecular discrepancies that may underpin rejection or other immune responses. GSEA indicated activation of the interferon-alpha response in memory T cells and suppression in CD4+ helper and γδ T cells, whereas TNFα signaling via NFκB was particularly active in regulatory T cells, γδ T cells, proliferating T cells, and activated CD8+ T cells. CellChat analysis revealed complex communication patterns within T-cell subsets, notably between proliferating T cells and activated CD8+ T cells. In conclusion, our study provides a comprehensive molecular landscape of T-cell diversity in islet transplantation. The insights into specific gene upregulation in xenotransplants suggest potential targets for improving graft tolerance. The differential pathway activation across T-cell subsets underscores their distinct roles in immune responses posttransplantation.

Human islets from deceased organ donors have made important contributions to our understanding of pancreatic endocrine function and continue to be an important resource for research studies aimed at understanding, treating, and preventing diabetes. Understanding the impacts of isolation and culture upon the yield of human islets for research is important for planning research studies and islet distribution to distant laboratories. Here, we examine islet isolation and cell culture outcomes at the Alberta Diabetes Institute (ADI) IsletCore (n = 197). Research-focused isolations typically have a lower yield of islet equivalents (IEQ), with a median of 252,876 IEQ, but a higher purity (median 85%) than clinically focused isolations before culture. The median recovery of IEQs after culture was 75%, suggesting some loss. This was associated with a shift toward smaller islet particles, indicating possible islet fragmentation, and occurred within 24 h with no further loss after longer periods of culture (up to 136 h). No overall change in stimulation index as a measure of islet function was seen with culture time. These findings were replicated in a representative cohort of clinical islet preparations from the Clinical Islet Transplant Program at the University of Alberta. Thus, loss of islets occurs within 24 h of isolation, and there is no further impact of extended culture prior to islet distribution for research.

Diabetes mellitus (DM) is a growing public health concern in South Africa (SA) and poses a substantial economic burden on healthcare globally. A century has passed since the discovery of insulin, and despite advances in diabetes management, exogenous insulin remains a primary treatment for type 1 DM, posing challenges of hyperglycaemia and hypoglycaemia. Pancreas transplantation should be considered a treatment for insulin-deficient DM, offering sustained euglycaemia and preventing complications associated with the disease. However, there has been a global decrease in the number of transplants performed. In SA, only a few pancreas transplants have been performed, primarily because of surgical risks and the need for immunosuppression. Islet transplantation is an alternative but faces limitations due to donor scarcity and immunosuppression requirements. This review explores recent progress in pancreas and islet transplants for DM, with the aim of providing insights into expanding treatment options for people with insulin-deficient DM.

NSG mice are among the most immunodeficient mouse model being used in various scientific branches. In diabetelogical research diabetic NSG mice are an important asset as a xenotransplantation model for human pancreatic islets or pluripotent stem cell-derived islets. The treatment with the beta cell toxin streptozotocin is the standard procedure for triggering a chemically induced diabetes. Surprisingly, little data has been published about the reproducibility, stress and animal suffering in these NSG mice during diabetes induction. The 3R rules, however, are a constant reminder that existing methods can be further refined to minimize suffering. In this pilot study the dose-response relationship of STZ in male NSG mice was investigated and additionally animal suffering was charted by applying the novel \'Relative Severity Assessment\' algorithm. By this we successfully explored an STZ dose that reliably induced diabetes while reduced stress and pain to the animals to a minimum using evidence-based and objective parameters rather than criteria that might be influenced by human bias.

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Diabetes mellitus, a significant global public health challenge, severely impacts human health worldwide. The organoid, an innovative in vitro three-dimensional (3D) culture model, closely mimics tissues or organs in vivo. Insulin-secreting islet organoid, derived from stem cells induced in vitro with 3D structures, has emerged as a potential alternative for islet transplantation and as a possible disease model that mirrors the human body\'s in vivo environment, eliminating species difference. This technology has gained considerable attention for its potential in diabetes treatment. Despite advances, the process of stem cell differentiation into islet organoid and its cultivation demonstrates deficiencies, prompting ongoing efforts to develop more efficient differentiation protocols and 3D biomimetic materials. At present, the constructed islet organoid exhibit limitations in their composition, structure, and functionality when compared to natural islets. Consequently, further research is imperative to achieve a multi-tissue system composition and improved insulin secretion functionality in islet organoid, while addressing transplantation-related safety concerns, such as tumorigenicity, immune rejection, infection, and thrombosis. This review delves into the methodologies and strategies for constructing the islet organoid, its application in diabetes treatment, and the pivotal scientific challenges within organoid research, offering fresh perspectives for a deeper understanding of diabetes pathogenesis and the development of therapeutic interventions.

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Pancreatic islet transplantation is an emerging treatment for type I diabetes; however, it is limited by donor matching and availability. Porcine islet xenotransplantation offers a promising alternative to allotransplantation, with the potential for large-scale production of on-demand, functional islets. The yield and viability of isolated islets is highly susceptible to the quality of the donor pancreas and the method of procurement, particularly the duration of warm-ischemia time. To improve organ preservation and subsequent islet yield and viability, we have developed a protocol for surgical perfusion and resection of the porcine pancreas. This protocol employs direct infrarenal aortic cannulation and organ perfusion to both minimize warm-ischemia time and simplify the procedure for operators who do not have extensive surgical expertise. Subsequent arterial perfusion of the pancreas via the aorta flushes stagnant blood from the microvasculature, thereby reducing thrombosis and oxidative damage to the tissue. This manuscript provides a detailed protocol for surgical perfusion and resection of the porcine pancreas, followed by islet isolation and purification.