Application of Genetically Modified and Cloned Pigs in Translational Research

Abstract

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.

Effect of Skin Fibroblast-Derived Allogeneic Feeder Cells on Porcine ES-Like Cell Establishment

“…However, continuous culture of pES-like cell lines developed on MEF and HFK feeders, represented a quick colony differentiation within a first few passages. In contrast, STO showed a better result for supporting undifferentiated growth of pES-like colonies, which was similar to previous reports [4,18,20]. Microenvironments produced from immortal STO cell lines may be more stable than those produced from mortal cell lines such as MEF and HFK.…”

“…The first stable ESC line was established from a mouse in 1981 [5,17], and since then stable ESC lines have also been generated in other species including primate monkeys [32] and humans [33]. These cells provide an effective approach to studying cell biology during embryogenesis, cell reprogramming and therapeutic applications for regenerative medicine.Porcine (p) ESCs have been demonstrated to have a remarkable potential for stem cell research from both the agricultural perspective and in biomedical fields principally due to the greater similarities in anatomy, physiology, immunology and lifespan with humans compared with mice and other species [11,18]. Although generation of pESC lines has been reported since 1990, no conclusive results have been obtained from the isolation and propagation of putative pESC lines [6,25,30].…”

Cloning and expression of porcine Dicer and the impact of developmental stage and culture conditions on MicroRNA expression in porcine embryos

“…The genetic modification of pigs, however, requires the use of assisted reproductive technologies (ART) such as somatic cell nuclear transfer. Even though interest has increased in producing large quantities of mature porcine oocytes and embryos for biomedical research purposes (Matsunari and Nagashima, 2009), embryos produced using ART and IVF procedures often exhibit aberrant development. Therefore, a need exists to characterize the role of miRNA in porcine embryonic development, as changes in the miRNA pathway may help explain altered embryonic development that occurs during the IVF production of embryos.…”

Production of CMAH Knockout Preimplantation Embryos Derived From Immortalized Porcine Cells Via TALE Nucleases

“…1,2,3,4 Somatic cell nuclear transfer (SCNT) with genetically modified somatic cells has been used to generate pig models via transgenesis. 5 Typical gene modifications are ectopic expression or knockout of target genes.…”