A novel biologic resorbable scaffold for tissue engineering of an intra-abdominal endocrine pancreas

摘要

Currently, islet transplantation has been generally performed in the liver, by intra-portal vein infusion. Islet transplants in this site, in a selected group of subjects with Type 1 diabetes, have shown excellent long-term function with stabilization of blood glucose levels and prevention of severe hypoglycemia. However, main limitations remain associated with the need for systemic immunosuppression to maintain function and with the observed loss of islet function over time. Additionally, several studies have demonstrated that the liver may not be the ideal site for islet transplantation due to several factors, including: (1) Instant Blood Mediated Inflammatory Reaction (IBMIR) following islet infusion responsible for the loss of over 50% of the transplanted islets; (2) potential procedure-related complications such as bleeding and thrombosis; (3) high levels of immunosuppressive drugs and GI toxins in the liver contributing to islet dysfunction; (4) the inability to retrieve islets after infusion. Based on these premises, we developed a novel transplant technology for the implantation of allogeneic human islets on the surface of the omentum, using a biodegradable biologic construct made of autologous plasma and human recombinant thrombin and minimizing any procedure-related "danger" signal that could activate pro-inflammatory reactions. The islets were re-suspended in autologous plasma and placed with "no-touch" technique on the surface of the omentum during a minimally invasive, laparoscopic surgical procedure. Pancreatic islet adherence to the omentum was achieved by addition of clinical-grade recombinant human thrombin to create a biocompatible, degradable gel containing the islet graft. The omentum was folded over the biologic scaffold and sealed by human recombinant thrombin. The first patient was transplanted on August 18,2015 using this technology (Phase Ⅰ/Ⅱ trial; clinicaltrials.gov NCT02213003) and has been free from insulin injections with an excellent glucose profile, following implantation of pancreatic islets obtained from a single donor pancreas. This was the first successful tissue engineered clinical islet transplant using a 'biodegradable scaffold' implanted on the surface of the omentum.