Pig–to–Non-human Primate Heart Transplantation: Immunologic Progress Over 20 Years

Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation (Impact Factor: 6.65). 04/2007; 26(3):210-8. DOI: 10.1016/j.healun.2006.12.005
Source: PubMed


The major developments in pig-to-non-human primate heart xenotransplantation during the past 20 years are summarized, largely through the experience of one investigator. Genetic modifications to organ-source pigs have been important steps in increasing heart xenograft survival from a few minutes in 1986 to 2 to 6 months in 2005.

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    • "Therefore, the use of tissue from a xenogeneic source has been considered for a long-time by many Asian ophthalmologists. Recently, pig has been widely studied as a possible donor for xenotransplantation, because the pig's organ size as well as its anatomy and physiology make it an ideal substitute as a xenograft (3-5). The feasibility of porcine cornea as a xenograft has currently been evaluated (6). "
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    ABSTRACT: Porcine to rat corneal xenotransplantation resulted in severe inflammation and rejection of the corneal stroma, whereas an allograft showed mainly endothelial cell-associated rejection. We, therefore, investigated and compared the gene expression between porcine keratocytes and corneal endothelial cells. RNA was isolated from primary cultured porcine or human keratocytes and porcine corneal endothelial cells. Gene expression was comparatively analyzed after normalization with microarray method using Platinum pig 13 K oligo chip (GenoCheck Co., Ltd., Ansan, Korea). Real-time polymerase chain reaction (PCR) was performed for C1R, CCL2, CXCL6, and HLA-A in porcine keratocytes and corneal endothelial cells. As a result, upregulated expression more than 2 folds was observed in 1,162 genes of porcine keratocytes versus porcine endothelial cells. Among the immune-regulatory genes, SEMA3C, CCL2, CXCL6, F3, HLA-A, CD97, IFI30, C1R, and G1P3 were highly expressed in porcine keratocytes, compared to porcine corneal endothelial cells or human keratocytes. When measured by real-time PCR, the expression of C1R, CCL2, and HLA-A was higher in porcine keratocytes compared to that in porcine corneal endothelial cells. In conclusion, the increased expression of C1R, CCL2, and HLA-A genes in porcine keratocytes might be responsible for the stromal rejection observed in a porcine to rat corneal xenotransplantation.
    Full-text · Article · May 2009 · Journal of Korean medical science
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    ABSTRACT: Baertschiger RM, Buhler LH. Xenotransplantation literature update March–April, 2007. Xenotransplantation 2007; 14: 360–365. © Blackwell Munksgaard, 2007
    No preview · Article · Jul 2007 · Xenotransplantation
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    ABSTRACT: Despite being still at the experimental level, xenotransplantation may become an effective strategy to overcome the scarcity of human organs. However, at the present time there is considerable resistance to this kind of biomedical technology. The aim of the present study was to identify novel strategies to reduce patients' negative affective reactions towards xenotransplantation helping them to understand the advantages of xenotransplantation in a more analytical fashion and increase their acceptance for this approach. The study was conducted in a group of patients with liver cirrhosis waiting for liver transplantation. They were presented with hypothetical scenarios and asked to choose among either two or three alternative types of donor defined by their species (e.g., livers from humans vs. other species) and availability (low for human donors and high for livers from non-human species). Patients were unwilling to accept xenotransplantation if they were presented with livers from humans (chosen by 97.5% of participants) vs. livers from genetically modified pigs (2.5%). On the other hand, a different group of patients was significantly more willing to accept xenotransplantation if they were presented with three different types of donors: respectively, human beings (74.4%), genetically modified pigs (25.6%) and genetically modified dogs. In addition, human livers were judged significantly more attractive than genetically modified livers from pigs, monkeys, dogs, or sheep and pig livers were rated as significantly more attractive than livers from monkeys, dogs, or sheep (for all comparisons P < 0.01). These results demonstrate that paradigms from other fields, like decision-making, might help to communicate more effectively the potential of xenotransplantation, modulating patients' affective reactions and allowing them to understand the potential strengths of this biomedical technology.
    No preview · Article · May 2008 · Xenotransplantation
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