Ex Vivo Gene Transfer for Improvement of Transplanted Pancreatic Islet Viability and Function

Authors: Linthout, S. V.1; Madeddu, P.1

Source: Current Pharmaceutical Design, Volume 11, Number 22, August 2005 , pp. 2927-2940(14)

Publisher: Bentham Science Publishers

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Abstract:

Human pancreatic islet transplantation has recently been shown to be successful in replacing pancreatic endocrine function into type 1 diabetic recipients. A major drawback, however, is the high amount of pancreatic ß cells required to render one single patient insulin-independent. Given the shortage of human ß cell donors, the majority of type 1 diabetic patients remain excluded from this therapeutic option. High number of islets are requested since substantial islet cell death and dysfunction occur within the first few hours and days after islet transplantation. Impaired vascularization of the engraft, the non-specific inflammatory reaction at the site of transplantation, together with the presence of active or memory autoimmune responses to islet autoantigens and allogeneic recognition contribute to apoptosis of ß cells and subsequent early graft function loss. This review will focus on ex vivo engineering of the islet graft by gene transfer to improve islet engraftment. An overview of currently used gene transfer techniques will be given and their potential will be discussed.

Keywords: ex vivo gene transfer; islets; engraftment; angiogenesis; diabetes

Document Type: Review article

DOI: 10.2174/1381612054546743

Affiliations: 1: Experimental Medicine and Gene Therapy Unit, INBB, Viale Sant'Antonio S.N.C., 07033 Osilo (SS),Italy.

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