Diabetes affects millions worldwide due to loss of functional insulin-producing β-cells. Current drug development is slow and costly, as preclinical models cannot continuously monitor human β-cell function in living organisms. The SILORGS project overcomes this hurdle by transplanting genetically engineered pancreatic islet organoids into the anterior chamber of the eye (ACE), a natural body window allowing longitudinal islet/organoid monitoring in vivo, non-invasively, at high-resolution. The organoids are equipped with biosensors that report β-cell activity in real time through fluorescent Ca2+ signals. Human islets and sensor organoids were transplanted into immunocompromised mice, with diabetes induced by a high-fat, high-sucrose diet (HFHSD) and selective β-cell ablation of in situ islets. Validation of the platform using the GLP-1 analogue liraglutide, as a proof-of-concept medication, demonstrated the ability of the platform to detect functional changes in β-cells, assess graft morphology and vascularization, and monitor treatment effects over time. SILORGS establishes a novel, integrated platform for early-stage drug testing, combining human tissue, genetic biosensors, and longitudinal in vivo imaging, with strong potential for commercial preclinical screening of anti-diabetic therapies.
Current preclinical models of diabetes primarily rely on systemic metabolic measurements, endpoint histology, or in vitro assays, which fail to capture the dynamic behavior of human pancreatic β-cells in vivo. This limitation reduces predictive accuracy, contributing to high failure rates in clinical translation and slowing the development of innovative therapies. A key unmet need is the ability to monitor human β-cell function longitudinally and non-invasively using sensor-enabled islet organoids, while simultaneously assessing systemic metabolic responses.
The SILORGS Proof of Concept project aimed at establishing and validating an industry-oriented in vivo imaging platform using genetically engineered sensor islet organoids transplanted into the ACE of recipient mice. The central milestone, achieved within 18 months, was the in vivo validation of these organoids as functional reporters for human β-cell activity in humanized diabetic mouse models, enabling standardized protocols for drug testing.
The project successfully generated fluorescent biosensor-integrated islet organoids, established humanized mouse models of diet-induced diabetes, and validated the platform using the GLP-1 analogue liraglutide. Functional in vivo imaging was combined with metabolic testing and longitudinal intravital analyses to evaluate β-cell activity, islet morphology, and vascularization.
The expected impact of SILORGS is threefold:
1. Scientific impact: Establishment of a novel in vivo functional imaging platform using sensor islet organoids as high-resolution reporters of human β-cell function.
2. Translational impact: Enhanced predictive power in early-stage drug development, potentially reducing costs and failure rates.
3. Commercial impact: Development of a scalable screening service for pharmaceutical companies focused on validating anti-diabetic lead compounds.
By enabling direct visualization of functional human β-cell responses in living organisms, SILORGS addresses a critical bottleneck in diabetes drug development and strengthens Europe’s position in translational biomedical innovation.
