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The potential of genetically-engineered pigs in providing an alternative source of organs and cells for transplantation

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The Journal of Biomedical Research 2013年第4期27卷 249-253页

作者： David K.C.Cooper Hidetaka Hara Mohamed Ezzelarab rita bottino Massimo Trucco Carol Phelps David Ayares Yifan Dai Thomas E.Starzl Transplantation Institute University of Pittsburgh Medical Center Division of Immunogenetics Children's Hospital of Pittsburgh University of Pittsburgh Revivicor Inc Jiangsu Key Laboratory of Xenotransplantation Nanjing Medical University

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.

关键词： pig blood transfusion pig genetic-engineered pig islets pig organs xenotransplantation

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Use of genetically-engineered pig donors in islet transplantation

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World Journal of Transplantation 2015年第4期5卷 243-250页

作者： rita bottino Massimo Trucco Institute of Cellular Thera-peutics Allegheny-Singer Research InstituteAllegheny Health Network

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 T1 D 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.

关键词： Genetic-engineering Diabetes Pig Islets Xenotransplantation

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A SYNDROME OF SEVERE HYPOGLYCEMIA AND ACIDOSIS IN YOUNG IMMUNOSUPPRESSED DIABETIC MONKEYS - ASSOCIATION WITH SEPSIS

A SYNDROME OF SEVERE HYPOGLYCEMIA AND ACIDOSIS IN YOUNG IMMU...

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2012中国器官移植大会

作者： Dirk J.van der Windt Eefje M.Dons Gabriel J. Echeverri Noriko Murase rita bottino Martin Wijkstrom Robert Wagner David K.C.Cooper Thomas E.Starzl Transplantation Institute Department of SurgeryUniversity of Pittsburgh Medical CenterPittsburghPAUSA Division of Immunogenetics Department of PediatricsChildren's Hospital of PittsburghPittsburghPAUSA

Large animals treated with immunosuppressive drug regimens for preclinical experiments of transplantation have increased risks of infection,as do individuals with *** we report our experience with severe sepsis in two young cynomolgus monkeys that were subjected to diabetes induction +/- islet *** both monkeys,infection was associated with a syndrome of profound hypoglycemia accompanied by severe *** the discussion of these cases we include information on five immunosuppressed pigs that also experienced severe hypoglycemic episodes after diabetes induction and islet

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