Transgenic Animals in Experimental Xenotransplantation Models: Orthotopic Heart Transplantation in the Pig-to-Baboon Model

Brandl, Ulrike; Michel, Sebastian; Erhardt, Matthias; Brenner, Paolo; Burdorf, Lars; Jöckle, H; Bittmann, Iris; Rössle, Matthias; Mordstein, Volker; Baschnegger, Heiko; Bauer, Andreas; Hammer, C.; Reichart, Bruno; Schmoeckel, Michael

doi:10.1016/j.transproceed.2006.12.021

Cited by 31 publications

(29 citation statements)

References 10 publications

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“…One proposed solution to this problem is xenotransplantation, in which non-human animal organs are transplanted into human patients. Research is currently being conducted to enable clinical implementation of this method, which will likely use pigs as organ donors for a variety of reasons [1,[84][85][86].…”

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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“…Despite their undoubted promise as sources of tissue transplants, many road blocks remain to using human ESC as a source of transplant material, especially as a means to test the efficacy of therapies and the safety of the transferred cells in animals whose anatomy and physiology better resemble the human than the mouse (11)(12)(13)(14)(15). The pig is a potentially useful model in this regard because of similarities in organ size, immunology, and whole animal physiology (16)(17)(18).…”

mentioning

confidence: 99%

Derivation of induced pluripotent stem cells from pig somatic cells

Ezashi¹,

Telugu²,

Alexenko³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

438

399

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For reasons that are unclear the production of embryonic stem cells from ungulates has proved elusive. Here, we describe induced pluripotent stem cells (iPSC) derived from porcine fetal fibroblasts by lentiviral transduction of 4 human (h) genes, hOCT4, hSOX2, hKLF4, and hc-MYC, the combination commonly used to create iPSC in mouse and human. Cells were cultured on irradiated mouse embryonic fibroblasts (MEF) and in medium supplemented with knockout serum replacement and FGF2. Compact colonies of alkaline phosphatase-positive cells emerged after Ϸ22 days, providing an overall reprogramming efficiency of Ϸ0.1%. The cells expressed porcine OCT4, NANOG, and SOX2 and had high telomerase activity, but also continued to express the 4 human transgenes. Unlike human ESC, the porcine iPSC (piPSC) were positive for SSEA-1, but negative for SSEA-3 and -4. Transcriptional profiling on Affymetrix (porcine) microarrays and real time RT-PCR supported the conclusion that reprogramming to pluripotency was complete. One cell line, ID6, had a normal karyotype, a cell doubling time of Ϸ17 h, and has been maintained through >220 doublings. The ID6 line formed embryoid bodies, expressing genes representing all 3 germ layers when cultured under differentiating conditions, and teratomas containing tissues of ectoderm, mesoderm, and endoderm origin in nude mice. We conclude that porcine somatic cells can be reprogrammed to form piPSC. Such cell lines derived from individual animals could provide a means for testing the safety and efficacy of stem cell-derived tissue grafts when returned to the same pigs at a later age.iPS ͉ reprogramming ͉ OCT4

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“…For passaging, the iPS cells were rinsed once with Hank's balanced salt solution (HBSS) (Invitrogen) and incubated in dissociation medium (ReproCELL) at 37 °C. All cultures were maintained at 37 °C in a humidified atmosphere containing 5% CO 2 .…”

Section: Microminipig Skin Tissuesmentioning

confidence: 99%

“…The pig is a potentially useful model in biomedical research because of similarities in its organ size, immunology, and whole animal physiology to those of humans [1][2][3][4]. However, the use of pigs and minipigs for in in vivo studies is difficult due to their heavy weight.…”

mentioning

confidence: 99%