Progress in Clinical Encapsulated Islet Xenotransplantation

Abstract

At the 2015 combined congress of the CTS, IPITA, and IXA, a symposium was held to discuss recent progress in pig islet xenotransplantation. The presentations focused on 5 major topics – (i) the results of 2 recent clinical trials of encapsulated pig islet transplantation, (ii) the inflammatory response to encapsulated pig islets, (iii) methods to improve the secretion of insulin by pig islets, (iv) genetic modifications to the islet-source pigs aimed to protect the islets from the primate immune and/or inflammatory responses, and (v) regulatory aspects of clinical pig islet xenotransplantation. Trials of microencapsulated porcine islet transplantation to treat unstable type 1 diabetic patients have been associated with encouraging preliminary results. Further advances to improve efficacy may include (i) transplantation into a site other than the peritoneal cavity, which might result in better access to blood, oxygen, and nutrients; (ii) the development of a more biocompatible capsule and/or the minimization of a foreign body reaction; (iii) pig genetic modification to induce a greater secretion of insulin by the islets, and/or to reduce the immune response to islets released from damaged capsules; and (iv) reduction of the inflammatory response to the capsules/islets by improvements in the structure of the capsules and/or in genetic-engineering of the pigs and/or in some form of drug therapy. Ethical and regulatory frameworks for islet xenotransplantation are already available in several countries, and there is now a wider international perception of the importance of developing an internationally-harmonized ethical and regulatory framework.

Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species

“…From a functional point of view, porcine islets respond to glucose stimulation with a 2-3-fold increase of insulin secretion whereas human islets show a 10-12-fold increase in response to a similar stimulation [5•]. This particularity of porcine beta cells probably explains the need to transplant a large number of islets (up to 50,000 IEQ/kg receiver body weight) [6,7] for the graft to produce physiologically relevant amounts of insulin. We and others [3, 8•] believe that neonatal pigs represent the most realistic source of islets for xenotransplantation in a clinical setting.…”

Renal xenotransplantation: experimental progress and clinical prospects

“…22 Clinical trials of pancreatic islet 23 and corneal xenotransplantation have already been performed in some parts of the world, and other trials are currently underway, but the governmental/legal framework in the US may be more stringent, particularly in regard to the transplantation of solid organs, such as the kidney.…”

Porcine Circoviruses and Xenotransplantation

“…Auckland Island pigs were used as source for the first clinical pig islet cell transplantation to human diabetic patients in New Zealand and Argentina [93,94,95,96]. These donor animals were free of PCV1 and PCV2, and therefore could not transmit circoviruses [94].…”