Genetic strategies to bring islet xenotransplantation to the clinic
- Author(s)
- Hawthorne, WJ; Lew, AM; Thomas, HE;
- Details
- Publication Year 2016-10,Volume 21,Issue #5,Page 476-83
- Journal Title
- Curr Opin Organ Transplant
- Publication Type
- Journal Article
- Abstract
- PURPOSE OF REVIEW: Despite the benefits of islet and pancreas allotransplantation, their widespread use in type 1 diabetes is limited because of the paucity of suitable donors. Porcine xenotransplantation offers an alternative, and advances in genetic modification of pigs have opened up new potential for its clinical use. This review outlines the barriers to successful islet xenotransplantation, and genetic modifications that have been tested to overcome these. RECENT FINDINGS: Islets from pigs lacking alpha1,3-galactosyltransferase, to prevent hyperacute rejection, are now used as a background strain for further genetic modifications. The instant blood-mediated inflammatory reaction is overcome by expressing complement regulators including CD46, CD55 and CD59. Prevention of immune-mediated rejection mediated by T cells, macrophages and natural killer cells remains a challenge. The use of immunosuppressive antibodies, such as anti-CD154 or anti-CD2, can be protective, and may be useful if they are produced by the islets themselves. SUMMARY: The field of xenotransplantation has benefited enormously from the development of new genetic modification strategies. With the possibility of multiple genetic modifications in the same animal, and a detailed knowledge of the mechanism of xenograft rejection, the challenge now is to develop islets that provide long-term graft survival without systemic immunosuppression.
- Publisher
- Wolters Kluwer
- Research Division(s)
- Immunology
- PubMed ID
- 27517501
- Publisher's Version
- https://doi.org/10.1097/MOT.0000000000000353
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-11-17 01:54:40
Last Modified: 2016-11-17 01:59:09