2681-P: Functional Assessment of EndoC-βH5 Cells In Vivo as a Model for Type 1 Diabetes in Humanized Mice

Introduction and Objective: The EndoC-βH5® represents an optimized, non-proliferative version of EndoC-βH1®, characterized by enhanced insulin secretion, functional response to incretin agonists through GLP1R and GIPR receptors and a phenotype close to human beta cell physiology. Current research highlights the urgent need for physiologically relevant human beta cell systems to study type I diabetes, such as in vivo humanized mice models. This study aimed to establish an in vivo humanized type I diabetes model using EndoC-βH5® cells. Methods: EndoC-βH5® cells were engrafted under the kidney capsule of immunodeficient NOD-Prkdcscid-IL2rgTm1/Rj mice. Following engraftment, blood glucose levels, clinical parameters, and plasma human C-peptide were monitored weekly for up to 7 weeks. At experimental endpoints, kidneys were harvested, paraffin-embedded, and analyzed for human insulin expression by immunofluorescence. Results: Mice engrafted with EndoC-βH5® exhibited stable glycemia during the initial observation period. Between days 40 and 54, human C-peptide levels ranged from 124 to 264 pM. Successful engraftment of EndoC-βH5® cells was confirmed by insulin immunostaining at the graft site. Conclusion: This study demonstrates the robust functional engraftment of EndoC-βH5® cells. EndoC-βH5® produced sustained insulin secretion in vivo without appearance of fatal hypoglycemia, validating it as a model relevant to study beta cells physiology. Disclosure K. Ho Wang Yin: None. M. Taurand: None. C. Chatellier: None. L. Joucla: None. H. Trouquet: None. B.C. Blanchi: None.