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World J Transplant. Dec 24, 2015; 5(4): 243-250
Published online Dec 24, 2015. doi: 10.5500/wjt.v5.i4.243
Use of genetically-engineered pig donors in islet transplantation
Rita Bottino, Massimo Trucco
Rita Bottino, Massimo Trucco, Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA 15212-4772, United States
Author contributions: Both authors equally contributed to this paper, including literature review, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Rita Bottino, Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, 320 East North Avenue, Pittsburgh, PA 15212-4772, United States. rbottino@wpahs.org
Telephone: +1-412-3596395 Fax: +1-412-3596987
Received: July 24, 2015
Peer-review started: July 27, 2015
First decision: September 22, 2015
Revised: October 23, 2015
Accepted: November 24, 2015
Article in press: November 25, 2015
Published online: December 24, 2015
Processing time: 152 Days and 4.4 Hours
Abstract

Type 1 diabetes (T1D) is an autoimmune disease wherein the pancreas does not produce enough insulin due to islet beta cell destruction. Despite improvements in delivering exogenous insulin to T1D patients, pancreas or islet transplantation remains the best way to regulate their glycaemia. Results from experimental islet transplantation have improved dramatically in the last 15 years, to the point where it can be comparable to pancreas transplantation, but without the accompanying morbidity associated with this procedure. As with other transplants, the limiting factor in islet allotransplantation is the relatively small number of organs made available by deceased human donors throughout the world. A strong case can be made for islet xenotransplantation to fill the gap between supply and demand; however, transplantation across species presents challenges that are unique to that setting. In the search for the most suitable animal for human xenotransplantation, the pig has many advantages that make it the likely animal of choice. Potentially one of the most beneficial advantages is the ability to genetically engineer porcine donors to be more compatible with human recipients. Several genetic manipulations have already proven useful in relation to hyperacute rejection and inflammation (instant blood mediated inflammatory reaction), with the potential of even further advancement in the near future.

Keywords: Genetic-engineering; Diabetes; Pig; Islets; Xenotransplantation

Core tip: Type 1 diabetes is widespread and debilitating. Islet allotransplantation from deceased human donors can reverse diabetes but there are too few donors to provide much help for more than a few recipients. Xenotransplantation of pig islets, readily obtainable in large quantities, can bridge this gap. Genetic manipulation of pigs in order to render their tissue more compatible with human recipients can improve graft function and would be necessary for clinical trials. Experience within the pig-to-nonhuman primate model help to determine the most beneficial enhancements, while technology evolves to provide improved techniques for multiple genetic manipulations.