Toward Engineering a Novel Transplantation Site for Human Pancreatic Islets

Abstract

Islet transplantation is a promising therapy for treatment of type 1 diabetes. A real breakthrough was reported when the Edmonton protocol was introduced in 2000. This protocol induced insulin independence in diabetic patients for 1 year (1). Although these clinical islet transplantations demonstrated the application of the technique, the long-term function of the islet grafts was not that successful. After 2 years, less than 50% of the patients remained insulin independent. Five years following transplantation, this declined to just 10% (1). In recent years, some groups demonstrated remarkable progress in islet transplantation outcomes (2), and experienced groups have been able to produce insulin independence after transplantation of islets from a single donor by controlling all known parameters for optimal islet donation (3). Recently, a number of groups have focused on the identification of factors determining success or failure of islet grafts. Various signs point to the transplantation site as a major factor in graft failure. The majority of islet transplantation is currently accomplished by the infusion of islets into the liver via the portal vein. Several alternative sites were investigated in animals and humans for efficacy as transplantation sites for islets, but none adequately accommodated islet engraftment. A rather novel approach that has been investigated recently is the engineering of an artificial site by using biopolymeric scaffolds. These scaffolds facilitate revascularization and allow adequate glucose sensing and insulin release. Recent developments in this area are reviewed in this article because of their potential clinical application. The exact causes of islet graft failure remain to be identified, but high metabolic pressure, recurring autoimmunity, and alloimmunity may be the basis of declining graft function over the long term (2,3). However, a key issue that cannot be explained by these responses is that the vast majority of islets are lost …