Subcutaneous Implantation of Open Microwell Islet Delivery Devices in Pigs

Abstract

Background Intraportal pancreatic islet transplantation is a treatment option for patients with severe beta cell failure and unstable glycemic control. However, this procedure is associated with loss of beta cells after intrahepatic transplantation. Islet delivery devices (IDDs) implanted at extrahepatic sites may support engraftment and improve survival of pancreatic islets. We assessed the surgical feasibility, tolerability and safety of implantation of open microwell devices at subcutaneous sites with varying friction in pigs. Methods Open, non-immunoisolating microwell islet delivery devices were made from polyvinylidene fluoride (PVDF). Empty (n = 26) and islet-seeded devices (n = 8) were implanted subcutaneously in 6 immunocompetent pigs in low-friction sites (abdomen and lateral hip) and high-friction sites (anterior neck) for 3 months. Retrieved grafts were analyzed histologically with haematoxylin and eosin, and Masson’s Trichrome staining. Results Islet-seeding and transportation of IDDs was free from complications with minimal islet spillage. IDDs were implanted subcutaneously using standard surgical equipment, without complications during the surgeries. IDDs implanted in the neck and IDDs co-transplanted with human islets were expelled and retrieved after 10 days. Empty IDDs were removed after 3 months. The abdominal site showed reduced signs of inflammation as compared to the neck region, while similar tissue ingrowth and vascularization of devices were found in the two locations. Conclusions Open microwell IDDs can safely be implanted with standard surgical equipment and successful islet-loading can be performed. Low-friction sites are preferable over high-friction sites for subcutaneous implantation in the porcine model since these lead to the least amount of foreign body reaction.