Islet cell transplantation: the future?

Abstract

Identification of obstacles to the success of islet transplantation, such as primary nonfunction, immunosuppression-related metabolic workload, or recurrence of autoimmunity, will allow the development of new strategies tailored to overcome them. In particular, novel immunosuppressive protocols, with or without the aim of inducing tolerance, and immunoisolation devices are reaching the stage of clinical applicability. Finally, several strategies, such as utilization of porcine xenogeneic islets or genetically engineered beta-cell lines, or in vitro expansion of cultured beta-cells could theoretically expand indefinitely the pool of islet tissue for transplantation.

Co-Expression of Vascular Endothelial Growth Factor and Interleukin-1 Receptor Antagonist Improves Human Islet Survival and Function

“…However, a large number of islets (>90,000 IE) are required to obtain insulin independence in clinical islet transplantation, requiring two to four cadaveric pancreata (1,2). This is because of the limited survival and function of transplanted islets in the host tissue (3). In this context, ex vivo gene therapy is a potential strategy to modify the biochemical environment in the immediate vicinity of the transplanted islets.…”

Bipartite Adenoviral Vector Encoding hHGF and hIL-1Ra for Improved Human Islet Transplantation

“…Thus, an enormous shortage of human islets is a barrier to the use of islet transplantation on a larger scale. Despite recent success, islet transplantation still lags behind primarily because a large number of transplanted islets often do not function (4). …”

Gene- and cell-based therapeutics for type I diabetes mellitus

“…[60][61][62][63] Recent advances in understanding transplantation immunology in general and the process of insulitis and the molecular/genetic bases of failure of central and/or New data suggest that a critical period between time of diagnosis and actual destruction of b-cell mass required for appropriate glycemic control (the so-called 'honeymoon period'; see below) may be exploited immunologically to obviate the need of islet transplantation altogether. While antibody-based approaches are currently being tested, it is anticipated that emerging gene and cell therapies can overcome the safety and negative systemic effects associated with the antibody approach.…”