• Asian-Australasian Journal of Animal Sciences
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• v.23 no.11
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• pp.1535-1542
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• 2010

Xenotransplantation is a hot topic currently, since the demand for diverse organs is increasing in patients. Among many species, pigs are suitable animals for xenotranplantation as they share many anatomical and physiological characteristics with humans. This review article provides an overview of porcine xenotransplantation and the rejection of pig xenotransplants in primates, and use of genetically modified and cloned pigs in xenotransplantation. It also highlights major target organs in porcine xenotransplantation and virus infection in xenotransplantation.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.10
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• pp.1497-1504
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• 2001

There is emerging interest in using xenotransplantation of porcine cells, tissues and organs for treatment of human illness. This article reviews the current status of xenotransplantation, with particular emphasis on the physiological and immunological barriers to xenotransplantation and genetic manipulations to overcome xenograft rejection. Preliminary success in xenotransplantation therapy for human Parkinson's disease using porcine foetal brain cells is described. Finally the zoonotic dangers of porcine xenotransplantation, most particularly porcine endogenous retroviruses (PERVs), are discussed.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2006.10a
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• pp.126-127
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• 2006

• Korean Journal of Veterinary Research
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• v.50 no.4
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• pp.273-277
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• 2010

The objective of this study was to investigate the infection rate of gastro-intestinal tract parasites on acquired laboratory nonhuman primates, Vervet monkey, Cynomolgus monkey, and Rhesus monkey acquired from Japan and China. These monkeys have been acclimating at an individual housing condition after our legal quarantine period. We examined 133 fecal samples to investigate parasitic infection using direct smear and formalin-ether-sedimentation technique. As a result, total parasitic infection rate was 33.8% (n = 45/133) for all monkeys. Two species of macaques, cynomolgus and rhesus, were infected with Trichuris trichiura (4), Giardia lamblia (4) and Balantidium coli (41). Vervet monkeys, which had been controlled by individual housing system for a long time, were clear for parasitic infection. The protozoan, Balantidium coli was one of the most frequently detected in these monkey colonies. Double infection was noted in only 4 monkeys and involved with Trichuris trichiura and Balantidium coli. Serious clinical symptoms were not observed in the most of the infected monkeys, but the monkeys infected by Giardia lamblia showed intermittent or chronic watery diarrhea. Consequently, the prophylactic anthelmintic treatment and periodic monitoring are essential to preserve the SPF colonies in the laboratory facility.

• Korean Circulation Journal
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• v.53 no.6
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• pp.351-366
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• 2023

Along with the development of immunosuppressive drugs, major advances on xenotransplantation were achieved by understanding the immunobiology of xenograft rejection. Most importantly, three predominant carbohydrate antigens on porcine endothelial cells were key elements provoking hyperacute rejection: α1,3-galactose, SDa blood group antigen, and N-glycolylneuraminic acid. Preformed antibodies binding to the porcine major xenoantigen causes complement activation and endothelial cell activation, leading to xenograft injury and intravascular thrombosis. Recent advances in genetic engineering enabled knock-outs of these major xenoantigens, thus producing xenografts with less hyperacute rejection rates. Another milestone in the history of xenotransplantation was the development of co-stimulation blockaded strategy. Unlike allotransplantation, xenotransplantation requires blockade of CD40-CD40L pathway to prevent T-cell dependent B-cell activation and antibody production. In 2010s, advanced genetic engineering of xenograft by inducing the expression of multiple human transgenes became available. So-called 'multi-gene' xenografts expressing human transgenes such as thrombomodulin and endothelial protein C receptor were introduced, which resulted in the reduction of thrombotic events and improvement of xenograft survival. Still, there are many limitations to clinical translation of cardiac xenotransplantation. Along with technical challenges, zoonotic infection and physiological discordances are major obstacles. Social barriers including healthcare costs also need to be addressed. Although there are several remaining obstacles to overcome, xenotransplantation would surely become the novel option for millions of patients with end-stage heart failure who have limited options to traditional therapeutics.

• IMMUNE NETWORK
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• v.4 no.1
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• pp.1-6
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• 2004

Transplantation would be the only way to cure the end-stage organ failure involving heart, lung, liver, kidney and pancreas. The replacement of the parts of the body damaged to lose its function or lost to trauma must be a dream of human-being. Human history is replete with chimeras, from sphinxes to mermaids, making one wonder if the ancients might actually have dreamed of what now is called 'xenotransplantation'. In the 20th century, the transplantation of organs and tissues to cure disease has become a clinical reality. The development in the fields of surgical techniques, physiology and immunology attributed to the successful transplantation in human. In the center of the successful transplantation lies the progress in understanding the cellular and molecular biology of immune system which led to the development of immunosuppressive drugs and the invention of the concept of immunological tolerance. The mandatory side effects of immunosuppressive drugs including infection and cancer forced us to search alternative approaches along with the development of new immunosuppressive agents. Among the alternative approaches, the induction of a state of immunologic tolerance would be the most promising and the most generic applicability as a future therapy. Recent reports documenting long-term graft survival without immunosuppression suggest that tolerance-based therapies may become a clinical reality. Last year, we saw the epoch making success of overcoming hyperacute rejection in porcine to primate xenotransplantation which will lead porcine to human xenotransplantation to clinical reality. In this review, I dare to summarize the development of transplantation immunology from the perspective of history.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.9-19
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• 2003

Pig organ is thought to be the most suitable nonhuman organ for xenotransplanstation. However, one of the major constraints to using pig organs for xenotransplantation is human natural antibody-mediated hyperacute rejection (HAR). Elimination of a(1,3) galactosyltransferase (GGTA1) from the pig is expected to be a solution to the problem of hyperacute rejection. Many efforts have made characterization of GGTA1 in structure and function, improvement in the technique of DNA transfection of somatic cells and advancement of the pig NT, a specific modification has been made to one copy of the GGTAl gene by Missouri group in 2002 To date because homozygousity of the genetic modification has been achieved in this gene, the role of gala(1,3) gal specific natural antibody in HAR and the efficacy of xenotransplantation in a nonhuman primate model will be addressed. Of other genes are found to be involved in rejection of pig donors by primates, the technology will be available to modify those genes so that rejection can be overcome.

• Journal of Embryo Transfer
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• v.30 no.4
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• pp.305-313
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• 2015

Xenotransplantation of pig islet regarded as a good alternative to allotransplantation. However, cellular death mediated by hypoxia-reoxygenation injury after transplantation disturb success of this technique. In the present study, we produce transgenic pig expressing human heme oxygenase 1 (HO1) genes to overcome cellular death for improving efficiency of islet xenotransplantation. Particularly, Korean miniature pig breed, Micro-Pig, was used in the present study. Somatic cell nuclear transfer (SCNT) technique was used to produce the HO1 transgenic pig. Six alive transgenic piglets were produced and all the transgenic pigs were founded to have transgene in their genomic DNA and the gene was expressed in all tested organs. Also, in vitro cultured fibroblasts derived from the HO1 transgenic pig showed low reactive oxygen species level, improved cell viability and reduced apoptosis level.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2003.10a
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• pp.9-19
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• 2003

Pig organ is thought to be the most suitable nonhuman organ for xenotransplanstation. However, one of the major constraints to using pig organs for xenotransplantation is human natural antibody-mediated hyperacute rejection (HAR). Elimination of a(1,3) galactosyltransferase (GGTA1) from the pig is expected to be a solution to the problem of hyperacute rejection. ry1any efforts have made characterization of GGTA1 in structure and function. improvement in the technique of DNA transfection of somatic cells and advancement of the pig NT, a specific modification has been made to one copy of the GGTA1 gene by Missouri group in 2002. To date because homozygousity of the genetic modification has been achieved in this gene, the role of gala(1,3) gal specific natural antibody in HAR and the efficacy of xenotransplantation in a nonhuman primate model will be addressed. If other genes are found to be involved in rejection of pig donors by primates, the technology will be available to modify those genes so that rejection can be overcome.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2004.10a
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• pp.83-84
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• 2004