Islet dimension and its impact on transplant outcome: A systematic review.

Background: Not all islet transplants desirably achieve insulin independence. This can be attributed to the microarchitecture and function of the islets influenced by their dimensions. Large islets enhance insulin secretion through paracrine effects but are more susceptible to hypoxic injury post-transplant, while small islets offer better viability and insulin independence. In vivo studies suggest large islets are essential for maintaining euglycemia, though smaller islets are typically preferred in transplantation for better outcomes.

Aim: To document the impact of islet dimension on clinical and preclinical transplant outcomes to optimize procedures.

Methods: PubMed, Scopus and EMBASE platforms were searched for relevant literature up to 9 April 2024. Articles reported on either glucose-stimulated insulin-secreting (GSIS) capacity, islet viability and engraftment, or insulin independence based on the islet dimension were included. The risk of bias was measured using the Appraisal Tool for Cross-Sectional Studies. Extracted data was analyzed via a narrative synthesis.

Results: Nineteen studies were included in the review. A total of sixteen studies reported the GSIS, of which nine documented the increased insulin secretion in the small islet, where the majority reported insulin secretion per islet equivalent (IEQ). Seven studies documented increased GSIS in large-sized islets that measure insulin secretion per cell or islet. All the articles that compared small and large islets reported poor viability and engraftment of large islets.

Conclusion: Small islets with a diameter < 125 µm have desired transplantation outcomes due to their better survival following isolation. Large-sized islets receive blood supply directly from arterioles in vivo to meet their higher metabolic demands. The large islet undergoes central necrosis soon after the isolation (devascularization); failing to maintain the viability and glucose stimuli leads to a decline in GSIS and the overall function of the islet. Improved preservation of large islets after islet isolation, enhances the islet yield (IEQ), thereby reducing the likelihood of failed islet isolation and potentially improves transplant outcome.