Progress and prospects: genetic engineering in xenotransplantation

Bas‐Bernardet, Stéphanie Le; Anegón, Ignacio; Blancho, Gilles

doi:10.1038/gt.2008.119

Cited by 27 publications

(25 citation statements)

References 35 publications

(53 reference statements)

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“…Pigs are considered the preferred donor species because their organ size is compatible with humans and because using non-human primate species poses difficult ethical concerns and infectious diseases (168, 177, 178). The development of genetically modified pigs expressing human complement pathway regulatory proteins (hCPRPs) or that have the α1,3-galactosyltransferase gene “knocked-out” (GalT-KO), has overcome the initial barriers posed by acute graft rejection (177–179). With these genetic modifications to inhibit recipient immunologic responses, porcine to non-human primate heart and kidney transplants have been successful (180).…”

Section: Transplantation Studiesmentioning

confidence: 99%

Porcine models of digestive disease: the future of large animal translational research

Gonzalez

Moeser

Blikslager

2015

Translational Research

185

167

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There is increasing interest in non-rodent translational models for the study of human disease. The pig, in particular, serves as a useful animal model for the study of pathophysiological conditions relevant to the human intestine. This review assesses currently used porcine models of gastrointestinal physiology and disease and provides a rationale for the use of these models for future translational studies. The pig has proven its utility for the study of fundamental disease conditions such as ischemia/ reperfusion injury, stress-induced intestinal dysfunction, and short bowel syndrome. Pigs have also shown great promise for the study of intestinal barrier function, surgical tissue manipulation and intervention, as well as biomaterial implantation and tissue transplantation. Advantages of pig models highlighted by these studies include the physiological similarity to human intestine as well as to mechanisms of human disease. Emerging future directions for porcine models of human disease include the fields of transgenics and stem cell biology, with exciting implications for regenerative medicine.

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Section: Transplantation Studiesmentioning

confidence: 99%

Porcine models of digestive disease: the future of large animal translational research

Gonzalez

Moeser

Blikslager

2015

Translational Research

185

167

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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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“…Consequently the ion channel does not form, the cell does not become lysed, and host cells will continue to live. According to [6].it has been suggested through experimentation that CD59 specifically binds only to C9 through its active site, which later inhibits the pore formation of the MAC [10]. The active site is suspected to be located in the vicinity of a hydrophobic groove from amino acid 16-57 and this section has been found to be the most conserved area of the protein and a mutation in this area can disrupt its function [7].…”

Section: Introductionmentioning

confidence: 99%