Abstract
Allogeneic islet transplantation into the liver has the potential to restore normoglycemia in patients with type 1 diabetes. However, the suboptimal microenvironment for islets in the liver is likely to be involved in the progressive islet dysfunction that is often observed post-transplantation. This study validates a novel microwell scaffold platform to be used for the extrahepatic transplantation of islet of Langerhans. Scaffolds were fabricated from either a thin polymer film or an electrospun mesh of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) block copolymer (composition: 4000PEOT30PBT70) and were imprinted with microwells, ∼400 µm in diameter and ∼350 µm in depth. The water contact angle and water uptake were 39±2° and 52.1±4.0 wt%, respectively. The glucose flux through electrospun scaffolds was three times higher than for thin film scaffolds, indicating enhanced nutrient diffusion. Human islets cultured in microwell scaffolds for seven days showed insulin release and insulin content comparable to those of free-floating control islets. Islet morphology and insulin and glucagon expression were maintained during culture in the microwell scaffolds. Our results indicate that the microwell scaffold platform prevents islet aggregation by confinement of individual islets in separate microwells, preserves the islet’s native rounded morphology, and provides a protective environment without impairing islet functionality, making it a promising platform for use in extrahepatic islet transplantation.
Highlights
Type 1 diabetes is characterized by the autoimmune-mediated destruction of insulin producing b-cells, resulting in absolute insulin deficiency
The aim of this study is to develop a novel non cell-adhesive, PEOT/PBT microwell scaffold platform to be used for extrahepatic islet transplantation
In contrast to exposure to extracts of natural rubber, which served as the positive control for cytotoxicity, nearly confluent monolayers were observed after exposure to extracts of polypropylene, polylactic acid films (PLA), and 4000PEOT30PBT70 films (Figure 2 A–B)
Summary
Type 1 diabetes is characterized by the autoimmune-mediated destruction of insulin producing b-cells, resulting in absolute insulin deficiency. Allogeneic islet transplantation in the liver via the infusion of islets into the portal vein has been explored as a potential therapy for patients with type 1 diabetes. Pancreata from at least two donors are required to achieve normoglycemia in a single patient and insulin independence lasts for only a few years, due to progressive islet loss in the post-transplantation period [3,4,6]. The islet loss is likely related to the consequences of their injection directly into the portal vein, where they are exposed to several stress factors such as high levels of immunosuppressive drugs, the instant blood-mediated inflammatory reaction (IBMIR), hyperglycemia, and low oxygen tension [7,8]
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