Will Genetic Engineering Carry Xenotransplantation of Pig Islets to the Clinic?

AbstractPurpose of ReviewPorcine islets represent a potentially attractive beta-cell source for xenotransplantation into patients with type 1 diabetes, who are not eligible to islet allo-transplantation due to a lack of suitable human donor organs. Recent progress in genetic engineering/gene editing of donor pigs provides new opportunities to overcome rejection of xeno-islets, to improve their engraftment and insulin secretion capacity, and to reduce the risk for transmission of porcine endogenous retroviruses. This review summarizes the current issues and progress in islet xenotransplantation with special emphasis on genetically modified/gene edited donor pigs.Recent FindingsAttempts to overcome acute rejection of xeno-islets, especially after intraportal transplantation into the liver, include the genetic elimination of specific carbohydrate antigens such as αGal, Neu5Gc, and Sd(a) for which humans and—in part—non-human primates have natural antibodies that bind to these targets leading to activation of complement and coagulation. A complementary approach is the expression of one or more human complement regulatory proteins (hCD46, hCD55, hCD59). T ransgenic attempts to overcome cellular rejection of islet xenotransplants include the expression of proteins that inhibit co-stimulation of T cells. Expression of glucagon-like peptide-1 and M3 muscarinic receptors has been shown to increase the insulin secretion of virally transduced porcine islet s in vitro and it will be...
Source: Current Diabetes Reports - Category: Endocrinology Source Type: research