Alginate-Catechol Cross-Linking Interferes with Insulin Secretion Capacity in Isolated Murine Islet Cells

Abstract

Over the past three decades, human pancreatic islet isolation and transplantation techniques have developed as a routine clinical procedure for selected patients with type 1 diabetes mellitus. However, due to the donor shortage and required chronic systemic immunosuppression, the widespread application of islet transplantation is limited. To overcome these limitations, providing a physical barrier to transplanted islet cells with encapsulating biomaterial has emerged as a promising approach to enhance engraftment and promote islet survival post-transplantation. Alginate has been considered to be a reliable biomaterial, as it enhances islet survival and does not hamper hormone secretion. Alginate-catechol (Al-CA) hydrogel was reported to provide high mechanical strength and chemical stability without deformation over a wide range of pH values. In this study, we, demonstrated, for the first time in the literature, that encapsulation of murine pancreatic islet cells with Al-CA hydrogel does not induce cytotoxicity ex vivo for an extended period; however, it does markedly abate glucose-stimulated insulin secretion. Catechol should not be considered as a constituent for alginate gelation for encapsulating islet cells in the application of islet transplantation.

Keywords: Alginic acid; Catechol; Diabetes mellitus, type 1; Hydrogel; Islets of Langerhans transplantation.

Fig. 1. Cytotoxicity test for encapsulated islet cells. Isolated murine islet cells were encapsulated with alginate hydrogel cross-linked either by calcium ion (Al-Ca²⁺) or catechol (alginate-catechol [Al-CA]). (A) Microscopic image of encapsulated islet cells with Al-CA hydrogel on the 7th day after the encapsulation. (B) Acridine orange and propidium iodide (PI) staining at different days post-encapsulation. No PI signal over 7 days post-encapsulation was detected. HA-ME+Col, hyaluronic methacrylate+collagen.

Fig. 2. Glucose-stimulated insulin secretion from encapsulated islet cells. Isolated murine islet cells were encapsulated with alginate hydrogel cross-linked by catechol (alginate-catechol [Al-CA]). (A) Free islet cells or encapsulated islet cells with Al-CA hydrogel (Al-CA encapsulated islets) were stimulated by 30 mM glucose for 30 minutes after 30-minute pre-incubation with 0 mM glucose. (B) Longer exposure to hyperglycemic milieu (30 mM) in both conditioned islet cells. ^aSignificantly higher than 0 mM glucose stimulation (P<0.001), ^bSignificantly lower than corresponding conditions in free islets (P<0.001), ^cSignificantly lower than corresponding conditions in free islets (P<0.001).