Exendin-4 Improves Yield and Function of Isolated Pre- Weaned Porcine Islets

Abstract

Background: orcine islets have been proposed as an alternative islet source for islet transplantation in patients with type 1 diabetes. Our focus on pre-weaned porcine islets (4-11 days old; PPIs) has shown that this model of porcine islets is a cost effective and viable mean to isolate and culture islets for transplantation. Exendin-4 (Ex4) could improve islet viability, islet expansion, and insulin secretion. PPIs are immature after islet isolation and the addition of growth factors could accelerate their maturation. This study investigated the effects of exposure to Ex-4 on the maturation of freshly isolated PPIs during in vitro culture. Methods: Pancreata from pre-weaned piglets (4-11 days old) were partially digested using low-dose collagenase and culture at 37°C and 5% CO2 for up to 3 days. 10nM of Ex-4 was added to culture media of freshly isolated PPIs. After 3-day culture, islets were assessed for islet yield, size, purity, membrane integrity, cellular viability and composition, and in vitro function. Results: Islet count (IC) was significantly higher in the Ex-4 group than in the control group. Islets treated with Ex-4 were significantly smaller than islets from the control group. The percentages of major endocrine cells (β-cells, α-cells, and δ-cells) were similar in both groups. Ex-4 supplementation significantly increased insulin secretion in response to glucose challenge. Conclusions: The addition of Ex-4 to culture media of freshly isolated PPIs could improve islet counts and produce islets with enhanced glucose-stimulated function. Culturing PPIs in Ex-4 could be beneficial to improve islet quality before transplantation.