The Choice of Anatomical Site for Islet Transplantation

Abstract

Islet transplantation into the portal vein is the current clinical practice. However, it has now been recognized that this implantation site has several characteristics that can hamper islet engraftment and survival, such as low oxygen tension, an active innate immune system, and the provocation of an inflammatory response (IBMIR). These factors result in the loss of many transplanted islets, mainly during the first hours or days after transplantation, which could in part explain the necessity for the transplantation of islets from multiple pancreas donors to cure type 1 diabetes. This increases the burden on the limited pool of donor organs. Therefore, an alternative anatomical site for islet transplantation that offers maximum engraftment, efficacious use of produced insulin, and maximum patient safety is urgently needed. In this review, the experience with alternative sites for islet implantation in clinical and experimental models is discussed. Subcutaneous transplantation guarantees maximum patient safety and has become clinically applicable. Future improvements could be achieved with innovative designs for devices to induce neovascularization and protect the islets from cellular rejection. However, other sites, such as the omentum, offer drainage of produced insulin into the portal vein for direct utilization in the liver. The use of pigs would not only overcome the shortage of transplantable islets, but genetic modification could result in the expression of human genes, such as complement regulatory or "anticoagulation" genes in the islets to overcome some site-specific disadvantages. Eventually, the liver will most likely be replaced by a site that allows long-term survival of islets from a single donor to reverse type 1 diabetes.

In situ application of hydrogel-type fibrin–islet composite optimized for rapid glycemic control by subcutaneous xenogeneic porcine islet transplantation

“…As a result, 60-70% of transplanted islets decay during the first few hours or days after transplantation [4]. Thus, alternative anatomical sites, including the omentum, spleen, renal capsule, bone marrow, intestinal gastric submucosa and skin, have been exploited to offer maximum engraftment, effective control of hyperglycemia and assurance of patient safety [5][6][7]. Among these, the subcutaneous space has been strongly suggested because of several attractive advantages, such as the greatest patient safety, an extensive surface area and easy implantation, re-transplantation and biopsy [7].…”

Transplantable bioartificial pancreas devices: current status and future prospects

“…Inflammatory reactions Islet transplantation is usually performed by intraportal delivery to the liver [61]. However, the exposure of isolated allogeneic or xenogeneic donor islets to the recipient's circulating blood triggers a rapid thromboinflammatory reaction termed instant blood-mediated inflammatory reaction (IBMIR).…”

“…The transplantation site for encapsulated islets is actually a controversial and highly critical issue to be considered. In clinical islet transplantation, free islets are commonly infused into the liver via the portal vein [61]. The insulin release from grafted islets into the portal circulation matches the physiologic route.…”

Bone marrow cavity: A supportive environment for islet engraftment

“…Most of these sites have not been well studied compared to the liver but a current review of the advantages and disadvantages of these various sites suggest they have no real benefit over the liver. 17,18 Our goal is to find a site that is both easily accessible and promotes islet function and survival. We have explored the bone marrow cavity as a site that might meet the above criteria.…”