The potential of genetically-engineered pigs in providing an alternative source of organs and cells for transplantation
Mohamed Ezzelarab is supported in part by the Joseph A. Patrick Research Fellowship in Transplantation of the Thomas E.Starzl Transplantation Institute of the University of Pittsburgh. Hidetaka Hara MD, PhD is supported in part by NIH grant # 1RO3A1096296-01. Studies on xenotransplantation at the Thomas E. Starzl Transplantation Institute are supported in part by CMRF (competitive medical research funding) from the University of Pittsburgh Medical Center, NIH grants # 1U19AI090959-01, # U01A1066331, and # 1PO1 HL107152, by an Ocular Tissue Engineering and Regenerative Ophthalmology (OTERO) Postdoctoral Fellowship, and by Sponsored Research Blacksburg, VA. Studies on xenotransplantation at the Nanjing Medical University are supported in part by a Sponsored Research Agreement between the Nanjing Medical University and Lung Biotechnology, Nanjing, China.
- Received Date: 2013-04-28
- Publish Date: 2013-07-28
- pig /
- blood transfusion; pig /
- genetic-engineered; pig /
- islets; pig /
- organs; xenotransplantation
Abstract: There is a critical shortage of organs, cells, and corneas from deceased human donors worldwide. There are also shortages of human blood for transfusion. A potential solution to all of these problems is the transplantation of organs, cells, and corneas from a readily available animal species, such as the pig, and the transfusion of red blood cells from pigs into humans. However, to achieve these ends, major immunologic and other barriers have to be overcome. Considerable progress has been made in this respect by the genetic modification of pigs to protect their tissues from the primate immune response and to correct several molecular incompatibilities that exist between pig and primate. These have included knockout of genes responsible for the expression of major antigenic targets for primate natural anti-pig antibodies, insertion of human complement- and coagulation-regulatory transgenes, and knockdown of swine leukocyte antigens that stimulate the primate's adaptive immune response. As a result of these manipulations, the administration of novel immunosuppressive agents, and other innovations, pig hearts have now functioned in baboons for 6-8 months, pig islets have maintained normoglycemia in diabetic monkeys for > 1 year, and pig corneas have maintained transparency for several months. Clinical trials of pig islet trans?plantation are already in progress. Future developments will involve further genetic manipulations of the organ-source pig, with most of the genes that are likely to be beneficial already identified.
|Citation:||David K.C. Cooper, Hidetaka Hara, Mohamed Ezzelarab, Rita Bottino, Massimo Trucco, Carol Phelps, David Ayares, Yifan Dai. The potential of genetically-engineered pigs in providing an alternative source of organs and cells for transplantation[J]. The Journal of Biomedical Research, 2013, 27(4): 249-253. doi: 10.7555/JBR.27.20130063|