SAT-620 Efficacy and Safety of In Vitro-Generated Insulin-Secreting Cell Infusion for Insulin-Dependent Diabetes Mellitus: A Systematic Review of Clinical Trials

Abstract Disclosure: L. Montejano: None. Y.S. Moura: None. L.H. Graciolli: None. L.P. Bertulessi: None. L.B. Mungai: None. F.J. Vasconcelos: None. J.F. Lopes: None. C.A. Erse: None. G.K. Silva: None. L.G. Fernandes: None. N.C. Rocha: None. K.D. Fontes: None. Introduction: Pancreatic islet transplantation has been extensively investigated as a therapeutic alternative for type 1 diabetes mellitus (T1DM), aiming to restore glycemic homeostasis through the reintroduction of functional beta cells. This systematic review synthesizes the available evidence on the efficacy and safety of this approach, considering data from recent clinical trials. Methods: A systematic literature review was conducted based on the PRISMA protocol, using the PubMed, Embase, and Cochrane databases. The search yielded 188 articles, and after deduplication, full-text screening, and application of inclusion and exclusion criteria, five articles were included for this study. These studies comprised clinical trials evaluating the efficacy and safety of pancreatic islet transplantation in patients with T1DM. Results: The analysis of the reviewed studies revealed sample sizes ranging from 4 to 20 patients. The evaluated interventions included the subcutaneous implantation of islet-derived cell aggregates, intrahepatic transplantation of isolated human pancreatic islets, and approaches involving stem cells differentiated into functional beta cells. Findings demonstrated substantial improvements in glycemic control, evidenced by reductions in glycated hemoglobin (HbA1c) levels and increased endogenous insulin secretion, measured by C-peptide stimulation assays. A progressive reduction in the need for exogenous insulin administration was observed, with a subset of patients achieving sustained insulin independence for periods of up to two years. The functional viability of the transplanted islets was confirmed through euglycemic-hyperinsulinemic clamp tests, demonstrating their ability to respond to exogenous glucose. However, graft survival varied among studies and was influenced by factors such as immunosuppressive regimen, cell viability at the time of infusion, and individual immunological characteristics of the patients. The main reported adverse events included T cell-mediated immune rejection, thromboembolic complications associated with the infusion site, and nephrotoxicity secondary to prolonged use of calcineurin inhibitors. Conclusion: Pancreatic islet transplantation is a promising T1DM treatment, yet challenges remain, such as limited donors, lifelong immunosuppression, and graft longevity variability. Future research should refine immunomodulation strategies and explore alternative beta cell sources to improve clinical outcomes. Presentation: Saturday, July 12, 2025