Hearts from transgenic pigs constructed with CD59/DAF genomic clones demonstrate improved survival in primates

Chen, Raymond H.; Naficy, Sephre; Logan, John S.; Diamond, Lisa E.; Adams, David H.

doi:10.1034/j.1399-3089.1999.00017.x

Cited by 95 publications

(49 citation statements)

References 19 publications

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“…Xenograft rejection comprises several steps, including hyperacute rejection, delayed xenograft rejection and cellular rejection [86]. To overcome these rejection reactions, multilayered genetic modification is required [87][88][89][90][91][92][93][94][95][96][97][98][99]. In other words, the complex mechanisms of xenograft rejection [91,92,100] must be countered by multiple gene modifications.…”

Section: Development Of Genetically Modified Pigs For Xenotransplantamentioning

confidence: 99%

Application of Genetically Modified and Cloned Pigs in Translational Research

Matsunari

Nagashima

2009

Journal of Reproduction and Development

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Abstract. Pigs are increasingly being recognized as good large-animal models for translational research, linking basic science to clinical applications in order to establish novel therapeutics. This article reviews the current status and future prospects of genetically modified and cloned pigs in translational studies. It also highlights pigs specially designed as disease models, for xenotransplantation or to carry cell marker genes. Finally, use of porcine somatic stem and progenitor cells in preclinical studies of cell transplantation therapy is also discussed. Key words: Cloned pig, Gene knockout, Transgenic pig, Translational research (J. Reprod. Dev. 55: [225][226][227][228][229][230] 2009) t present, pigs are not only considered important livestock but are also essential large-animal models in various types of biomedical research [1][2][3][4][5][6]. Furthermore, due to recent technological advances in genetic modification and somatic cell cloning, the range of applications for porcine models has increased markedly [7][8][9][10][11][12][13][14]. The present review focuses on development of genetically modified and cloned pigs and their use in translational studies.Translational research plays an important role as a bridge between basic science outcomes and the clinical realm, leading to development of novel therapeutics. However, disparate findings for rodent models and humans have hindered the translation of rodent data into actionable technologies for patients [15]. In contrast, pigs have many anatomical and physiological similarities to humans, including their cardiovascular systems, omnivorous gastrointestinal tracts and central nervous systems. Their physical sizes are also more comparable to that of humans, rendering pigs more appropriate for development of new surgical or endoscopic techniques.In the future, more advanced translational research may be conducted by improving the clinical relevance of pig models through genetic engineering. This article reviews the current status and future prospects of genetically modified pigs in preclinical studies of stem and progenitor cell therapy, the development of disease models and xenotransplantation.

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Section: Development Of Genetically Modified Pigs For Xenotransplantamentioning

confidence: 99%

Application of Genetically Modified and Cloned Pigs in Translational Research

Matsunari

Nagashima

2009

Journal of Reproduction and Development

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“…Some progress has been made towards prolonging xenograft survival (2). For example, organs from pigs genetically modified to express human complement regulatory proteins are capable of controlling activation of primate complement and are thus protected from hyperacute rejection in primates (3)(4)(5). However, all pig-toprimate vascularized grafts are ultimately rejected within days to months, depending on the treatment protocol, by a process termed acute vascular rejection or delayed xenograft rejection (2).…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Recombinant Human Antithrombin III in Pig-to-Primate Renal Xenotransplantation

Cowan

Aminian

Barlow

et al. 2002

American Journal of Transplantation

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Delayed rejection of pig kidney xenografts by primates is associated with vascular injury that may be accompanied by a form of consumptive coagulopathy in recipients. Using a life-supporting pig-to-baboon renal xenotransplantation model, we have tested the hypothesis that treatment with recombinant human antithrombin III would prevent or at least delay the onset of rejection and coagulopathy. Non-immunosuppressed baboons were transplanted with transgenic pig kidneys expressing the human complement regulators CD55 and CD59. Recipients were treated with an intravenous infusion of antithrombin III eight hourly (250 units per kg body weight), with or without low molecular weight heparin. Antithrombin-treated recipients had preservation of normal renal function for 4-5 days, which was twice as long as untreated animals, and developed neither thrombocytopenia nor significant coagulopathy during this period. Thus, recombinant antithrombin III may be a useful therapeutic agent to ameliorate both early graft damage and the development of systemic coagulation disorders in pig-to-human xenotransplantation.

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“…To overcome immunological barriers, transgenic pigs bearing human complement-inhibiting proteins have been developed, leading to increased control of hyperacute rejection in primate models (8,13,19,24,31,41,47; M. Winkler, M. Loss, M. Przemeck, J. Schmidtko, H. Arends, R. Kunz, A. Jalali, J. Klempnauer, E. Cozzi, and D. J. G. White, Abstr. 5th Int.…”

mentioning

confidence: 99%