Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
REVIEW

Somatic cell nuclear transfer in pigs: recent achievements and future possibilities

Gábor Vajta A D , Yunhai Zhang A B and Zoltán Macháty C
+ Author Affiliations
- Author Affiliations

A Population Genetics and Embryology, Department of Genetics and Biotechnology, Danish Institute of Agricultural Sciences, DK-8830 Tjele, Denmark.

B College of Animal Sciences and Technology, Anhui Agricultural University, Hefei City, Anhui Province 230036, China.

C Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.

D Corresponding author. Email: gabor.vajta@agrsci.dk

Reproduction, Fertility and Development 19(2) 403-423 https://doi.org/10.1071/RD06089
Submitted: 30 August 2006  Accepted: 24 October 2006   Published: 29 January 2007

Abstract

During the past 6 years, considerable advancement has been achieved in experimental embryology of pigs. This process was mainly generated by the rapidly increasing need for transgenic pigs for biomedical research purposes, both for future xenotransplantation to replace damaged human organs or tissues, and for creating authentic animal models for human diseases to study aetiology, pathogenesis and possible therapy. Theoretically, among various possibilities, an established somatic cell nuclear transfer system with genetically engineered donor cells seems to be an efficient and reliable approach to achieve this goal. However, as the result of unfortunate coincidence of known and unknown factors, porcine embryology had been a handicapped branch of reproductive research in domestic animals and a very intensive and focused research was required to eliminate or minimise this handicap. This review summarises recent achievements both in the background technologies (maturation, activation, embryo culture) and the actual performance of the nuclear replacement. Recent simplified methods for in vivo development after embryo transfer are also discussed. Finally, several fields of potential application for human medical purposes are discussed. The authors conclude that although in this early phase of research no direct evidence can be provided about the practical use of transgenic pigs produced by somatic cell nuclear transfer as organ donors or disease models, the future chances even in medium term are good, and at least proportional with the efforts and sums that are invested into this research area worldwide.

Additional keywords: disease model, porcine, transgenic, xenotransplantation.


Acknowledgements

The authors thank Cesare Galli, Irina Lagutina, Heiner Niemann, Randall S. Prather, Rongfeng Li, Scott Davis, Yutao Du, Li Juan, and Teija T. Peura for supporting this review by sharing their unpublished data with us.


References

Abeydeera, L. R. (2002). In vitro production of embryos in swine. Theriogenology 57, 257–273.
CrossRef | PubMed |

Abeydeera, L. R. , Wang, W. H. , Cantley, T. C. , Rieke, A. , Prather, R. S. , and Day, B. N. (1998). Presence of epidermal growth factor during in vitro maturation of pig oocytes and embryo culture can modulate blastocyst development after in vitro fertilization. Mol. Reprod. Dev. 51, 395–401.
CrossRef | PubMed |

Abeydeera, L. R. , Wang, W. H. , Cantley, T. C. , Rieke, A. , Murphy, C. N. , Prather, R. S. , and Day, B. N. (2000). Development and viability of pig oocytes matured in a protein-free medium containing epidermal growth factor. Theriogenology 54, 787–797.
CrossRef | PubMed |

Algriany, O. , Bevers, M. , Schoevers, E. , Colenbrander, B. , and Dieleman, S. (2004). Follicle size-dependent effects of sow follicular fluid on in vitro cumulus expansion, nuclear maturation and blastocyst formation of sow cumulus oocytes complexes. Theriogenology 62, 1483–1497.
CrossRef | PubMed |

Alisky, J. M. (2004). Xenografts are an achievable breakthrough. Med. Hypotheses 63, 92–97.
CrossRef | PubMed |

Andersson L. (2005). Historical perspective biology of the pig and relevance to medicine. In ‘Proceedings of the Swine in Biomedical Research Conference’, 27–29 Januray 2005, Chicago, IL. p. 39.

Bauer, A. , Baschnegger, H. , Abicht, J. M. , Brandl, U. , and Brenner, P. , et al. (2005). hDAF procine cardiac xenograft maintains cardiac output after orthotopic transplantation into baboon – a perioperative study. Xenotransplantation 12, 444–449.
CrossRef | PubMed |

Betthauser, J. , Forsberg, E. , Augenstein, M. , Childs, L. , and Eilertsen, K. , et al. (2000). Production of cloned pigs from in vitro systems. Nat. Biotechnol. 18, 1055–1059.
CrossRef | PubMed |

Boelhauve, M. , Sinowatz, F. , Wolf, E. , and Paula-Lopes, F. F. (2005). Maturation of bovine oocytes in the presence of leptin improves development and reduces apoptosis of in vitro-produced blastocysts. Biol. Reprod. 73, 737–744.
CrossRef | PubMed |

Bondioli, K. R. , Ramsoondar, J. J. , Williams, B. L. , Costa, C. , and Fodor, W. L. (2001). Cloned pigs generated from cultured skin fibroblasts derived from a H-transferase transgenic boar. Mol. Reprod. Dev. 60, 189–195.
CrossRef | PubMed |

Booth, P. J. , Tan, S. J. , Holm, P. , and Callesen, H. (2001). Application of the zona-free manipulation technique to porcine somatic nuclear transfer. Cloning Stem Cells 3, 191–197.
CrossRef | PubMed |

Booth, P. J. , Holm, P. , and Callesen, H. (2005). The effect of oxygen tension on porcine embryonic development is dependent on embryo type. Theriogenology 63, 2040–2052.
CrossRef | PubMed |

Boquest, A. C. , Grupen, C. G. , Harrison, S. J. , McIlfatrick, S. M. , Ashman, R. J. , d'Apice, A. J. , and Nottle, M. B. (2002). Production of cloned pigs from cultured fetal fibroblast cells. Biol. Reprod. 66, 1283–1287.
CrossRef | PubMed |

Bucher, P. , Morel, P. , and Bühler, L. H. (2005). Xenotransplantation: an update on recent progress and future perspectives. Transpl. Int. 18, 894–901.
CrossRef | PubMed |

Calise, F. , Mancini, A. , Amoroso, P. , Belli, A. , and Bracco, A. , et al. (2001). Functional evaluation of the AMC-BAL to be employed in a multicentric clinical trial for acute liver failure. Transplant. Proc. 33, 647–649.
CrossRef | PubMed |

Chen, G. , Zian, H. , Starzl, T. , Sun, H. , and Garcia, B. , et al. (2005). Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys. Nat. Med. 11, 1295–1298.
CrossRef | PubMed |

Choi, Y. H. , Love, L. B. , Westhusin, M. E. , and Hinrichs, K. (2004). Activation of equine nuclear transfer oocytes: methods and timing of treatment in relation to nuclear remodeling. Biol. Reprod. 70, 46–53.
CrossRef | PubMed |

Clark, J. , and Whitelaw, B. (2003). A future for transgenic livestock. Nat. Rev. Genet. 4, 825–833.
CrossRef | PubMed |

Craig, J. , Zhu, H. , Dyce, P. W. , Petrik, J. , and Li, J. (2004). Leptin enhances oocyte nuclear and cytoplasmic maturation via the mitogen-activated protein kinase pathway. Endocrinology 145, 5355–5363.
CrossRef | PubMed |

Craig, J. A. , Zhu, H. , Dyce, P. W. , Wen, L. , and Li, J. (2005). Leptin enhances porcine preimplantation embryo development in vitro. Mol. Cell. Endocrinol. 229, 141–147.
CrossRef | PubMed |

Cui, X. S. , Lee, J. Y. , Choi, S. H. , Kwon, M. S. , Kim, T. , and Kim, N. H. (2004). Mouse granulocyte-macrophage colony-stimulating factor enhances viability of porcine embryos in defined culture conditions. Anim. Reprod. Sci. 84, 169–177.
CrossRef | PubMed |

Dai, Y. , Vaught, T.D. , Boone, J. , Chen, S.-H. , and Phelps, C. J. , et al. (2002). Targeted disruption of the α-1,3-galactosyltransferase gene in cloned pigs. Nat. Biotechnol. 20, 251–255.
CrossRef | PubMed |

Day B., Abeydeera L., and Prather R. (2000). Recent progress in pig embryo production through in vitro maturation and feritilization techniques. In ‘Proceedings IV International Conference on Boar Semen Preservation’. (Eds G. La and H. D. Johnson.) pp. 81–92. (Allen Press: Lawrence, KS.)

Deacon, T. , Schumacher, J. , Dinsmore, J. , Thomas, C. , and Palmer, P. , et al. (1997). Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson’s disease. Nat. Med. 3, 350–353.
CrossRef | PubMed |

de la Fuente, R. , and King, W. A. (1998). Developmental consequences of karyokinesis without cytokinesis during the first mitotic cell cycle in bovine parthenotes. Biol. Reprod. 58, 952–962.
CrossRef | PubMed |

Deschamps, J. Y. , Roux, F. A. , Saï, P. , and Gouin, E. (2005a). History of xenotransplantation. Xenotransplantation 12, 91–109.
CrossRef | PubMed |

Deschamps, J. Y. , Roux, F. A. , Gouin, E. , and Sai, P. (2005b). Reluctance of French patients with type 1 diabetes to undergo pig pancreatic islet cell xenotransplantation. Xenotransplantation 12, 175–180.
CrossRef | PubMed |

De Sousa, P. A. , Dobrinsky, J. R. , Zhu, J. , Archibald, A. L. , and Ainslie, A. , et al. (2002). Somatic cell nuclear transfer in the pig: control of pronuclear formation and integration with improved methods for activation and maintenance of pregnancy. Biol. Reprod. 66, 642–650.
CrossRef | PubMed |

Di Nicuolo, G. , van de Kerkhove, M. P. , Hoekstra, R. , Beld, M. G. , and Amoroso, P. , et al. (2005). No evidence of in vitro and in vivo porcine endogenous retrovirus infection after plasmapheresis through the ACM bioartificial liver. Xenotransplantation 12, 286–292.
CrossRef | PubMed |

Dinsmore, J. H. , Manhart, C. , Raineri, R. , Jacoby, D. B. , and Moore, A. (2000). No evidence for infection of human cells with porcine endogenous retrovirus (PERV) after exposure to porcine fetal neuronal cells. Transplantation 70, 1382–1389.
CrossRef | PubMed |

Du, Y. , Kragh, P. M. , Zhang, X. , Purup, S. , Yang, H. , Bolund, L. , and Vajta, G. (2005). High overall in vitro efficiency of porcine handmade cloning (HMC) combining partial zona digestion and oocyte trisection with sequential culture. Cloning Stem Cells 7, 199–205.
CrossRef | PubMed |

Esaki, R. , Ueda, H. , Kurome, M. , Hirakawa, K. , Tomii, R. , Yoshioka, H. , Ushijima, H. , Kuwayama, M. , and Nagashima, H. (2004). Cryopreservation of porcine embryos derived from in vitro-matured oocytes. Biol. Reprod. 71, 432–437.
CrossRef | PubMed |

Eventov-Friedman, S. , Katchman, H. , Shezen, E. , Aronovich, A. , Tchorsh, D. , Dekel, B. , Freud, E. , and Reisner, Y. (2005). Embryonic pig liver, pancreas and lung as a source for transplantation: optimal organogenesis without teratome depends on distinct time-windows. Proc. Natl Acad. Sci. USA 102, 2928–2933.
CrossRef | PubMed |

Ezzelarab, M. , and Cooper, D. K. C. (2005). Reducing Gal expression on the pig organ – a retrospective review. Xenotransplantation 12, 278–285.
CrossRef | PubMed |

Forsberg E. J. (2005). Genetically modified swine. In ‘Proceedings of the Swine in Biomedical Research Conference’, 27–29 January 2005, Chicago, IL. p. 40.

Fujimura, T. , Kurome, M. , Murakami, H. , Takahagi, Y. , and Matsunami, K. , et al. (2004). Cloning of the transgenic pigs expressing human decay accelerating factor and N-acetylglucosaminyltransferase III. Cloning Stem Cells 6, 294–301.
PubMed |

Fujita, F. , Yamashita-Futsuki, I. , Eguchi, S. , Kamohara, Y. , Fujioka, H. , and Yanaga, K. (2003). Inactivation of porcine endogenous retrovirus by human serum as a function of complement activated through the classical pathway. Hepatol. Res. 26, 106–113.
CrossRef | PubMed |

Funahashi, H. , Cantley, T. C. , and Day, B. N. (1997). Synchronization of meiosis in porcine oocytes by exposure to dibutyryl cyclic adenosine monophosphate improves developmental competence following in vitro fertilization. Biol. Reprod. 57, 49–53.
CrossRef | PubMed |

Galili, U. (2005). The α-gal epitope and the anti-Gal antibody in xenotransplantation and in cancer immunotherapy. Immunol. Cell Biol. 83, 674–686.
CrossRef | PubMed |

Galili, U. , Mandrell, R. E. , Hamadeh, R. M. , Shohet, S. B. , and Griffiss, J. M. (1988). Interaction between human natural anti-alpha-galactosyl immunoglobulin G and bacteria of the human flora. Infect. Immun. 56, 1730–1737.
PubMed |

Galli, C. , Lagutina, I. , and Lazzari, G. (2003a). Introduction to cloning by nuclear transfer. Cloning Stem Cells 5, 223–232.
CrossRef | PubMed |

Galli, C. , Lagutina, I. , Crotti, G. , Colleoni, S. , Turini, P. , Ponderato, N. , Duchi, R. , and Lazzari, G. (2003b). Pregnancy: a cloned horse born to its dam twin. Nature 424, 635.
CrossRef | PubMed |

Garcia, B. , Sun, H. T. , Yang, H. J. , Chen, G. , and Zhong, R. (2004). Xenotransplantation of human decay accelerating factor porcine kidney to non-human primates: 4 years experience at a Canadian center. Transplant. Proc. 36, 1714–1716.
CrossRef | PubMed |

Garkavenko, O. , Croxson, M. C. , Irgang, M. , Karlas, A. , Denner, J. , and Elliott, R. B. (2004). Monitoring for presence of potentially xenotic viruses in recipients of pig islet xenotransplantation. J. Clin. Microbiol. 42, 5353–5356.
CrossRef | PubMed |

Gautier, J. , Minshull, J. , Lohka, M. , Glotzer, M. , Hunt, T. , and Maller, J. L. (1990). Cyclin is a component of maturation-promoting factor from Xenopus. Cell 60, 487–494.
CrossRef | PubMed |

Gerrity, R. G. , Natarajan, R. , Nadler, J. L. , and Kimsey, T. (2001). Diabetes-induced accelerated atherosclerosis in swine. Diabetes 50, 1654–1665.
PubMed |

Ghosh, F. , Wong, F. , Johansson, K. , Bruun, A. , and Petters, R. M. (2004). Transplantation of full-thickness retina in the rhodopsin transgenic pig. Retina 24, 98–109.
CrossRef | PubMed |

Goldman, I. G. , Kadulin, S. , and Razin, S. V. (2004). Transgenic animals in medicine: integration and expression of foreign genes, theoretical and applied aspects. Med. Sci. Monit. 10, RA274–RA285.
PubMed |

Good, H. , Cooper, D. K. C. , Malcolm, A. J. K. , Ippolito, R. M. , Koren, E. , Neethling, F. A. , Ye, Y. , Zyhdi, N. , and Lamontagne, L. R. (1992). Identification of carbohydrate structures which bind human anti-porcine antibodies: implications for discordant grafting in man. Transplant. Proc. 24, 559–562.
PubMed |

Gregersen, N. , Bolund, L. , and Bross, P. (2005). Protein misfolding, aggregation, and degradation in disease. Mol. Biotechnol. 31, 141–150.
CrossRef | PubMed |

Groth, C. G. , Korsgren, O. , Tibell, A. , Tollemar, J. , Moller, E. , Bolinder, J. , Ostman, J. , Reinholt, F. P. , Hellerstrom, C. , and Andersson, A. (1994). Transplantation of porcine fetal pancreas to diabetic patients. Lancet 344, 1402–1404.
CrossRef | PubMed |

Grupen, C. G. , Nagashima, H. , and Nottle, M. B. (1997). Role of epidermal growth factor and insulin-like growth factor-I on porcine oocyte maturation and embryonic development in vitro. Reprod. Fertil. Dev. 9, 571–575.
CrossRef | PubMed |

Hagelin, J. (2004). Public opinion surveys about xenotransplantation. Xenotransplantation 11, 551–558.
CrossRef | PubMed |

Hammer, C. , and Thein, E. (2002). Physiological aspects of xenotransplantation, 2001. Xenotransplantation 9, 303–305.
CrossRef | PubMed |

Harrison, S. , Boquest, A. , Grupen, C. , Faast, R. , and Guildolin, A. , et al. (2004). An efficient method for producing alpha(1,3)-galactosyltransferase gene knockout pigs. Cloning Stem Cells 6, 327–331.
CrossRef | PubMed |

Hasler-Rapacz, J. , Ellegren, H. , Fridolfsson, A. K. , Kirpatrick, B. , Kirk, S. , Andersson, L. , and Rapacz, J. (1998). Identification of a mutation in the low density lipoprotein receptor gene associated with recessive familial hypercholesterinemia in swine. Am. J. Med. Genet. 76, 379–386.
CrossRef | PubMed |

Hölker, M. , Petersen, B. , Hassel, P. , Kues, W. A. , Lemme, E. , Lucas-Hahn, A. , and Niemann, H. (2005). Duration of in vitro maturation of recipient oocytes affects blastocyst development of cloned porcine embryos. Cloning Stem Cells 7, 35–44.
CrossRef | PubMed |

Hoshino, Y. , Uchida, M. , Shimatsu, Y. , Miyake, M. , Nagao, Y. , Minami, N. , Yamada, M. , and Imai, H. (2005). Developmental competence of somatic cell nuclear transfer embryos reconstructed from oocytes matured in vitro with follicle shells in miniature pig. Cloning Stem Cells 7, 17–26.
CrossRef | PubMed |

Houser, S. L. , Kuwaki, K. , Knosalla, C. , Dor, F. J. , Gollackner, B. , Cheng, J. , Shimizu, A. , Schuurman, H. J. , and Cooper, D. K. (2004). Thrombotic microangiopathy and graft arteriopathy in pig hearts following transplantation into baboons. Xenotransplantation 11, 416–425.
CrossRef | PubMed |

Hunter, C. V. , Tiley, L. S. , and Sang, H. M. (2005). Development in transgenic technology: applications for medicine. Trends Mol. Med. 11, 293–298.
CrossRef | PubMed |

Hunter, R.H. (2002). Vital aspects of fallopian tube physiology in pigs. Reprod. Domest. Anim. 37, 186–190.
CrossRef | PubMed |

Hunter, R. H. , Polge, C. , and Rowson, L. E. (1967). The recovery, transfer and survival of blastocysts in pigs. J. Reprod. Fertil. 14, 501–502.
PubMed |

Hyun, S. H. , Lee, G. S. , Kim, D. Y. , Kim, H. S. , and Lee, S. H. , et al. (2003a). Effect of maturation media and oocytes derived from sows or gilts on the development of cloned pig embryos. Theriogenology 59, 1641–1649.
CrossRef | PubMed |

Hyun, S. , Lee, G. , Kim, D. , Kim, H. , and Lee, S. , et al. (2003b). Production of nuclear transfer-derived piglets using porcine fetal fibroblasts transfected with the enhanced green fluorescent protein. Biol. Reprod. 69, 1060–1068.
CrossRef | PubMed |

Ierino, F. L. , Kozlowski, T. , Siegel, J. B. , Shimizu, A. , and Colvin, R. B. , et al. (1998). Disseminated intravascular coagulation in association with the delayed rejection of pig-to-baboon renal xenografts. Transplantation 66, 1439–1450.
CrossRef | PubMed |

Im, G. S. , Lai, L. , Liu, Z. , Hao, Y. , Wax, D. , Bonk, A. , and Prather, R. S. (2004). In vitro development of preimplantation porcine nuclear transfer embryos cultured in different media and gas atmospheres. Theriogenology 61, 1125–1135.
CrossRef | PubMed |

Inverardi, L. , Clissi, B. , Stolzer, A. , Bender, J. R. , Sandrin, M. S. , and Pardi, R. (1997). Human natural killer lymphocytes directly recognize evolutionarily conserved oligosaccharide ligands expressed by xenogeneic tissues. Transplantation 63, 1318–1324.
CrossRef | PubMed |

Irgang, M. , Sauer, I. M. , Karlas, A. , Zeilinger, K. , Gerlach, J. C. , Kurth, R. , Neuhaus, P. , and Denner, J. (2003). Porcine endogenous retroviruses: no infection in patients treated with a bioreactor based on porcine liver cells. J. Clin. Virol. 28, 141–154.
CrossRef | PubMed |

Iwamoto, M. , Onishi, A. , Fuchimoto, D. , Somfai, T. , and Takeda, K. , et al. (2005). Low oxygen tension during in vitro maturation of porcine follicular oocytes improves parthenogenetic activation and subsequent development to the blastocyst stage. Theriogenology 63, 1277–1289.
CrossRef | PubMed |

Jeong, Y. J. , Kim, J. G. , Mohana Kumar, B. , Balasubramanian, S. , Choe, S. Y. , and Rho, G. J. (2006). Effects of leptin on in vitro development and gene expression in porcine embryos. Reprod. Fertil. Dev. 18, 246–247.
CrossRef |

Karja, N. W. , Wongsrikeao, P. , Murakami, M. , Agung, B. , Fahrudin, M. , Nagai, T. , and Otoi, T. (2004). Effects of oxygen tension on the development and quality of porcine in vitro fertilized embryos. Theriogenology 62, 1585–1595.
CrossRef | PubMed |

Karlas, A. , Kurth, R. , and Denner, J. (2004). Inhibition of porcine endogenous retroviruses by RNA interference: increasing the safety of xenotransplantation. Virology 325, 18–23.
CrossRef | PubMed |

Kawakami, M. , Tani, T. , Yabuuchi, A. , Kobayashi, T. , Murakami, H. , Fujimura, T. , Kato, Y. , and Tsunoda, Y. (2003). Effect of demecolcine and nocodazole on the efficiency of chemically assisted removal of chromosomes and the developmental potential of nuclear transferred porcine oocytes. Cloning Stem Cells 5, 379–387.
CrossRef | PubMed |

Kidson, A. , Rubio-Pomar, F. J. , Van Knegsel, A. , Van Tol, H. T. , Hazeleger, W. , Ducro-Steverink, D. W. , Colenbrander, B. , Dieleman, S. J. , and Bevers, M. M. (2004). Quality of porcine blastocysts produced in vitro in the presence or absence of GH. Reproduction 127, 165–177.
CrossRef | PubMed |

Kikuchi, K. , Onishi, A. , Kashiwazaki, N. , Iwamoto, M. , Noguchi, J. , Kaneko, H. , Akita, T. , and Nagai, T. (2002). Successful piglet production after transfer of blastocysts produced by a modified in vitro system. Biol. Reprod. 66, 1033–1041.
CrossRef | PubMed |

Kim, H. S. , Lee, G. S. , Hyun, S. H. , Lee, S. H. , Nam, D. H. , Jeong, Y. W. , Kim, S. , Kang, S. K. , Lee, B. C. , and Hwang, W. S. (2004). Improved in vitro development of porcine embryos with different energy substrates and serum. Theriogenology 61, 1381–1393.
CrossRef | PubMed |

Kim, H. S. , Lee, G. S. , Hyun, S. H. , Nam, D. H. , and Lee, S. H. , et al. (2005a). Embryotropic effect of glycosaminoglycans and receptors in development of porcine pre-implantation embryos. Theriogenology 63, 1167–1180.
CrossRef | PubMed |

Kim, H. S. , Lee, G. S. , Kim, J. H. , Kang, S. K. , Lee, B. C. , and Hwang, W. S. (2006a). Expression of leptin ligand and receptor and effect of exogenous leptin supplement on in vitro development of porcine embryos. Theriogenology 65, 831–844.
CrossRef | PubMed |

Kim, J. H. , Lee, S. H. , Kim, S. , Jeong, Y. W. , and Koo, O. J. , et al. (2006b). Embryotrophic effects of ethylenediaminetetraacetic acid and hemoglobin on in vitro porcine embryos development. Theriogenology 66, 449–455.
CrossRef | PubMed |

Kim, J. S. , Koo, D. B. , Song, B. S. , Wee, G. B. , Lee, K. K. , and Han, Y. M. (2006c). Improved mitochondrial membrane potential and preimplantation development of porcine embryos by dibutyryl cAMP treatment. Reprod. Fertil. Dev. 18, 192.
CrossRef |

Kim, S. , Lee, G. S. , Lee, S. H. , Kim, H. S. , Jeong, Y. W. , Kim, J. H. , Kang, S. K. , Lee, B. C. , and Hwang, W. S. (2005b). Embryotropic effect of insulin-like growth factor (IGF)-I and its receptor on development of porcine preimplantation embryos produced by in vitro fertilization and somatic cell nuclear transfer. Mol. Reprod. Dev. 72, 88–97.
CrossRef | PubMed |

Kitagawa, Y. , Suzuki, K. , Yoneda, A. , and Watanabe, T. (2004). Effects of oxygen concentration and antioxidants on the in vitro developmental ability, production of reactive oxygen species (ROS), and DNA fragmentation in porcine embryos. Theriogenology 62, 1186–1197.
CrossRef | PubMed |

Kolber-Simonds, D. , Lai, L. , Watt, S. R. , Denaro, M. , and Arn, S. , et al. (2004). Production of α-1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations. Proc. Natl Acad. Sci. USA 101, 7335–7340.
CrossRef | PubMed |

Kragh, P. M. , Vajta, G. , Corydon, T. J. , Purup, S. , Bolund, L. , and Callesen, H. (2004). Production of transgenic porcine blastocysts by hand-made cloning. Reprod. Fertil. Dev. 16, 315–318.
CrossRef | PubMed |

Kragh, P. M. , Du, Y. , Corydon, J. , Purup, S. , Bolund, L. , and Vajta, G. (2005). Efficient in vitro production of porcine blastocysts by handmade cloning with combined electric and chemical activation. Theriogenology 64, 1536–1545.
CrossRef | PubMed |

Kranenburg, L. W. , Kerssens, C. , Ijzermans, N. J. , Zuidema, W. , Weimar, W. , and Busschbach, J. J. (2005). Reluctant acceptance of xenotransplantation in kidney patients on the waiting list for transplantation. Soc. Sci. Med. 61, 1828–1834.
CrossRef | PubMed |

Kues, W. A. , and Niemann, H. (2004). The contribution of farm animals to human health. Trends Biotechnol. 22, 286–294.
CrossRef | PubMed |

Kühholzer, B. , Tao, T. , Macháty, Z. , Hawley, R. J. , Greenstein, J. L. , Day, B. N. , and Prather, R. S. (2000). Production of transgenic porcine blastocysts by nuclear transfer. Mol. Reprod. Dev. 56, 145–148.
CrossRef | PubMed |

Kurome, M. , Ueda, H. , Tomii, R. , Naruse, K. , and Nagashima, H. (2006). Production of transgenic-clone pigs by the combination of ICSI-mediated gene transfer with somatic cell nuclear transfer. Transgenic Res. 15, 229–240.
CrossRef | PubMed |

Kuwaki, K. , Tseng, Y.-L. , Dor, F. J. , Shimizu, A. , and Houser, S. L. , et al. (2005). Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat. Med. 11, 29–31.
CrossRef | PubMed |

Lagutina, I. , Lazzari, G. , and Galli, C. (2006). Birth of cloned pigs from zona-free nuclear transfer blastocysts developed in vitro before transfer. Cloning Stem Cells 8, 283–293.
CrossRef | PubMed |

Lai, L. , Park, K. W. , Cheong, H. T. , Kühholzer, B. , and Samuel, M. , et al. (2002a). Transgenic pig expressing the enhanced green fluorescent protein produced by nuclear transfer using colchicine-treated fibroblasts as donor cells. Mol. Reprod. Dev. 62, 300–306.
CrossRef | PubMed |

Lai, L. , Kolber-Simonds, D. , Park, K.-W. , Cheong, H.-T. , and Greenstein, J. L. , et al. (2002b). Production of α-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295, 1089–1092.
CrossRef | PubMed |

Lai, L. , Kang, J. X. , Li, R. , Wang, J. , and Witt, W. T. , et al. (2006). Generation of cloned transgenic pigs rich in omega-3 fatty acids. Nat. Biotechnol. 24, 435–436.
CrossRef | PubMed |

Ledford, H. (2006). The farmyard drug store. Nature 443, 16–17.
CrossRef | PubMed |

Lee, G. S. , Hyun, S. H. , Kim, H. S. , Kim, D. Y. , Lee, S. H. , Lim, J. M. , Lee, E. S. , Kang, S. K. , Lee, B. C. , and Hwang, W. S. (2003a). Improvement of a porcine somatic cell nuclear transfer technique by optimizing donor cell and recipient oocyte preparations. Theriogenology 59, 1949–1957.
CrossRef | PubMed |

Lee, G. S. , Kim, H. S. , Hyun, S. H. , Lee, S. H. , and Jeon, H. Y. , et al. (2005a). Production of transgenic cloned piglets from genetically transformed fetal fibroblasts selected by green fluorescent protein. Theriogenology 63, 973–991.
CrossRef | PubMed |

Lee, J. W. , Wu, S. C. , Tian, X. C. , Barber, M. , Hoagland, T. , Riesen, J. , Lee, K. H. , Tu, C. F. , Cheng, W. T. , and Yang, X. (2003b). Production of cloned pigs by whole-cell intracytoplasmic microinjection. Biol. Reprod. 69, 995–1001.
CrossRef | PubMed |

Lee, M. S. , Kang, S. K. , Lee, B. C. , and Hwang, W. S. (2005b). The beneficial effects of insulin and metformin on in vitro developmental potential of porcine oocytes and embryos. Biol. Reprod. 73, 1264–1268.
CrossRef | PubMed |

Lee, S. H. , Kim, D. Y. , Nam, D. H. , Hyun, S. H. , Lee, G. S. , Kim, H. S. , Lee, C. K. , Kang, S. K. , Lee, B. C. , and Hwang, W. S. (2004). Role of messenger RNA expression of platelet activating factor and its receptor in porcine in vitro-fertilized and cloned embryo development. Biol. Reprod. 71, 919–925.
CrossRef | PubMed |

Li, G. P. , Tan, J. H. , Sun, Q. Y. , Meng, Q. G. , Yue, K. Z. , Sun, X. S. , Li, Z. Y. , Wang, H. B. , and Xu, L. B. (2000). Cloned piglets born after nuclear transplantation of embryonic blastomeres into porcine oocytes matured in vivo. Cloning 2, 45–52.
CrossRef | PubMed |

Li N., Lian Z., Pei D. Z., Zhang X., Zhang Q., and Zhao X. (2005). Chinese experimental pig models for human disease and xenotransplantation. In ‘Proceedings of the Swine in Biomedical Research Conference’, 27–29 January 2005, Chicago, IL. p. 22.

Li, R. , Lai, L. , Wax, D. , Hao, Y. , and Murphy, C. , et al. (2006). Cloned transgenic swine via in vitro production and cryopreservation. Biol. Reprod. 75, 226–230.
CrossRef | PubMed |

Lin, S. S. , Kooyman, D. L. , Daniels, L. J. , Dagget, C. W. , and Parker, W. , et al. (1997). The role of natural anti Galα1–3Gal antibodies in hyperacute rejection of pig-to-baboon cardiac xenotransplants. Transplant. Immunol 5, 212–218.
CrossRef |

Lin, S. S. , Weidner, B. C. , Byrne, G. W. , Diamond, L. E. , and Lawson, J. H. , et al. (1998). The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants. J. Clin. Invest. 101, 1745–1756.
PubMed |

Logan, J. S. (2000). Prospects of xenotransplantation. Curr. Opin. Immunol. 12, 563–568.
CrossRef | PubMed |

Lorca, T. , Cruzalegui, F. H. , Fesquet, D. , Cavadore, J. C. , Mery, J. , Means, A. , and Doree, M. (1993). Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs. Nature 366, 270–273.
CrossRef | PubMed |

Lu, Q. , Han, H. , Lia’n, Z. , Li, N. , Zhang, Q. , Zhao, Z. , Pei, D. , Zhang, X. , and Wu, C. (2004). The screening and identification of endogenous retrovirus free CEMPs. Sci. China C Life Sci. 47, 562–566.
CrossRef | PubMed |

Macháty, Z. , and Prather, R. S. (1998). Strategies for activating nuclear transfer oocytes. Reprod. Fertil. Dev. 10, 599–613.
CrossRef | PubMed |

Macháty, Z. , Day, B. N. , and Prather, R. S. (1998). Development of early porcine embryos in vitro and in vivo. Biol. Reprod. 59, 451–455.
CrossRef | PubMed |

Macháty, Z. , Bonk, A. J. , Kühholzer, B. , and Prather, R. S. (2000). Porcine oocyte activation induced by a cytosolic sperm factor. Mol. Reprod. Dev. 57, 290–295.
CrossRef | PubMed |

Magre, S. , Takeuchi, Y. , and Bartosch, B. (2003). Xenotransplantation and pig endogenous retroviruses. Rev. Med. Virol. 13, 311–329.
CrossRef | PubMed |

Manez, R. , Lopez-Pealez, E. , Centeno, A. , Herrera, J. M. , Juffe, A. , Domenech, N. , Harrison, R. , and Schuurman, H. J. (2004). Transgenic expression in pig hearts of both human decay-accelerating factor and human membrane cofactor protein does not provide an additional benefit to that of human decay-accelerating factor alone in pig-to-baboon xenotransplantation. Transplantation 78, 930–933.
CrossRef | PubMed |

Marchal, R. , Vigneron, C. , Perreau, C. , Bali-Papp, A. , and Mermillod, P. (2002). Effect of follicular size on meiotic and developmental competence of porcine oocytes. Theriogenology 57, 1523–1532.
CrossRef | PubMed |

Martin, U. , Tacke, S. J. , Simon, A. , Schroder, C. , Wiebe, K. , Lapin, B. , Haverich, A. , Denner, J. , and Steinhoff, G. (2002). Absence of PERV specific humoral immune response in baboons after transplantation of porcine cells or organs. Transplant. Int. 15, 361–368.
CrossRef |

McEvoy, T. G. , Alink, F. M. , Moreira, V. C. , Watt, R. G. , and Powell, K. A. (2006). Embryo technologies and animal health – consequences for the animal following ovum pick-up, in vitro embryo production and somatic cell nuclear transfer. Theriogenology 65, 926–942.
CrossRef | PubMed |

McGregor, C. G. , Teotia, S. S. , Byrne, G. V. , Michaels, M. G. , Risdahl, J. M. , Schirmer, J. M. , Tazelaar, H. D. , Walker, R. C. , and Logan, J. S. (2004). Cardiac xenotransplantation: progress toward the clinic. Transplantation 78, 1569–1575.
CrossRef | PubMed |

McGregor, C. G. , Davies, W. R. , Oi, K. , Teotia, S. S. , and Schirmer, J. M. , et al. (2005). Cardiac xenotransplantation: recent preclinical progress with 3-month median survival. J. Thorac. Cardiovasc. Surg. 130, 844–851.
CrossRef | PubMed |

McKane, B. W. , Ramachandran, S. , Yang, J. , Xu, X. C. , and Mohanakumar, T. (2003). Xenoreactive anti-Galα(1,3)Gal antibodies prevent porcine endogenous retrovirus infection of human in vivo. Hum. Immunol. 64, 708–717.
CrossRef | PubMed |

Medvedev, S. , Onishi, A. , Fuchimoto, D. , Iwamoto, M. , and Nagai, T. (2004). Advanced in vitro production of pig blastocysts obtained through determining the time for glucose supplementation. J. Reprod. Dev. 50, 71–76.
CrossRef | PubMed |

Men, H. , Agca, Y. , Critser, E. S. , and Critser, J. K. (2005). Beneficial effects of serum supplementation during in vitro production of porcine embryos on their ability to survive cryopreservation by open pulled straw vitrification. Theriogenology 64, 1340–1349.
CrossRef | PubMed |

Michie, C. (2001). Xenotransplantation, endogenous pig retroviruses and the precautionary principle. Trends Mol. Med. 7, 62–63.
CrossRef | PubMed |

Milan, D. , Jeon, J. T. , Looft, C. , Amarger, V. , and Robic, A. , et al. (2000). A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle. Science 288, 1248–1251.
CrossRef | PubMed |

Milland, J. , Christiansen, D. , and Sandrin, M. (2005). α-1, 3-galactosyltransferase knockout pigs are available for xenotransplantation: are glycosyltransferases still relevant? Immunol. Cell Biol. 83, 687–693.
CrossRef | PubMed |

Miyagawa, S. , Nakatsu, S. , Nakagawa, T. , Kondo, A. , Matsunami, K. , Hazama, K. , Yamada, J. , Tomonaga, K. , Miyazawa, T. , and Shirakura, R. (2005). Prevention of PERV infections in pig to human xenotransplantation by the RNA interference silences gene. J. Biochem. 137, 503–508.
PubMed |

Miyoshi, K. , Saeki, K. , and Sato, E. (2000). Improvement in development of porcine embryos reconstituted with cells from blastocyst-derived cell lines and enucleated oocytes by optimization of reconstruction methods. Cloning 2, 175–184.
CrossRef | PubMed |

Miyoshi, K. , Rzucidlo, S. J. , Pratt, S. L. , and Stice, S. L. (2003). Improvements in cloning efficiencies may be possible by increasing uniformity in recipient oocytes and donor cells. Biol. Reprod. 68, 1079–1086.
CrossRef | PubMed |

Morgan, A. , and Jacob, R. (1994). Ionomycin enhances Ca2+ influx by stimulating store-regulated cation entry and not by a direct action at the plasma membrane. Biochem. J. 300, 665–672.
PubMed |

Nagashima, H. , Kashiwazaki, N. , Ashman, R. J. , Grupen, C. , and Nottle, M. B. (1995). Cryopreservation of porcine embryos. Nature 374, 416.
CrossRef | PubMed |

Nagashima, H. , Fujimura, T. , Takahagi, Y. , Kurome, M. , and Wako, N. , et al. (2003). Development of efficient strategies for the production of genetically modified pigs. Theriogenology 59, 95–106.
CrossRef | PubMed |

Nam, D. H. , Lee, S. H. , Kim, H. S. , Lee, G. S. , Jeong, Y. W. , Kim, S. , Kim, J. H. , Kang, S. K. , Lee, B. C. , and Hwang, W. S. (2005). The role of gonadotropin-releasing hormone (GnRH) and its receptor in development of porcine preimplantation embryos derived from in vitro fertilization. Theriogenology 63, 190–201.
CrossRef | PubMed |

Niemann, H. , and Rath, D. (2001). Progress in the reproductive biotechnology in swine. Theriogenology 56, 1291–1304.
CrossRef | PubMed |

Nishitai, R. , Ikai, I. , Shiotani, T. , Katsura, N. , Matsushita, T. , Yamanokuchi, S. , Matsuo, K. , Sugimoto, S. , and Yamaoka, Y. (2005). Absence of PERV infection in baboons after transgenic porcine liver perfusion. J. Surg. Res. 124, 45–51.
CrossRef | PubMed |

Oback, B. , Wiersema, A. T. , Gaynor, P. , Laible, G. , and Tucker, F. C. , et al. (2003). Cloned cattle derived from a novel zona-free embryo reconstruction system. Cloning Stem Cells 5, 3–12.
CrossRef | PubMed |

Ock, S. A. , Kim, J. G. , Shi, L. Y. , Jin, H. F. , Mohana Kumar, B. , Choe, S. Y. , and Rho, G. J. (2005). Comparison of development and quality of porcine embryos cultured in different oxygen concentrations. Reprod. Fertil. Dev. 17, 223.
CrossRef |

Oldmixon, B. A. , Wood, J. C. , Ericcson, T. A. , Wilson, C. A. , White-Scharf, M. E. , Andersson, G. , Greenstein, J. L. , Schuurman, H. J. , and Patience, C. (2002). Porcine endogenous retrovirus transmission characteristics of an inbred herd of miniature swine. J. Virol. 76, 3045–3048.
CrossRef | PubMed |

Onishi, A. , Iwamoto, M. , Akita, T. , Mikawa, S. , Takeda, K. , Awata, T. , Hanada, H. , and Perry, A. C. (2000). Pig cloning by microinjection of fetal fibroblast nuclei. Science 289, 1188–1190.
CrossRef | PubMed |

Palmarini, M. , and Fan, H. (2001). Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer. J. Natl. Cancer Inst. 93, 1603–1614.
PubMed |

Pan, D. , Zhang, Y. , Sun, X. , Zhang, J. , Li, X. , Li, Y. , Gu, Z. , Dai, Y. , Wu, C. , and Li, N. (2006). Cloned pigs derived from somatic cell nuclear transfer embryos cultured in vitro at low oxygen tension. Chin. Sci. Bull. 51, 839–844.
CrossRef |

Paradis, K. , Langford, G. , Long, Z. , Heneine, W. , and Sandstrom, P. , et al. (1999). Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. Science 285, 1236–1241.
CrossRef | PubMed |

Park, J. I. , Hong, J. Y. , Yong, H. Y. , Hwang, W. S. , Lim, J. M. , and Lee, E. S. (2005). High oxygen tension during in vitro oocyte maturation improves in vitro development of porcine oocytes after fertilization. Anim. Reprod. Sci. 87, 133–141.
CrossRef | PubMed |

Park, K. W. , Cheong, H. T. , Lai, L. X. , Im, G. S. , and Kühholzer, B. , et al. (2001). Production of nuclear transfer-derived swine that express the enhanced green fluorescent protein. Anim. Biotechnol. 12, 173–181.
CrossRef | PubMed |

Park, K. W. , Lai, L. , Cheong, H. T. , Cabot, R. , and Sun, Q. Y. , et al. (2002). Mosaic gene expression in nuclear transfer-derived embryos and the production of cloned transgenic pigs from ear-derived fibroblasts. Biol. Reprod. 66, 1001–1005.
CrossRef | PubMed |

Park, M. R. , Cho, S. K. , Park, J. Y. , Lee, S. Y. , Choi, Y. J. , Kwon, D. N. , Son, W. J. , Seo, H. G. , and Kim, J. H. (2004). Detection of rare Leydig cell hypoplasia in somatic cell cloned male piglets. Zygote 12, 305–313.
CrossRef | PubMed |

Pascher, A. , Sauer, I. , Hammer, C. , Gerlach, J. , and Neuhaus, P. (2002). Extracorporeal liver perfusion as hepatic asist in acute liver failure: a review of world experience. Xenotransplantation 9, 309–324.
CrossRef | PubMed |

Paterson, L. , DeSousa, P. , Ritchie, W. , King, T. , and Wilmut, I. (2003). Application of reproductive biotechnology in animals: implications and potentials. Application of reproductive cloning. Anim. Reprod. Sci. 79, 137–143.
CrossRef | PubMed |

Patience, C. , Takeuchi, Y. , and Weiss, R. A. (1997). Infection of human cells by an endogenous retrovirus of pigs. Nat. Med. 3, 282–286.
CrossRef | PubMed |

Peters, J. M. (2002). The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol. Cell 9, 931–943.
CrossRef | PubMed |

Petters, R. M. , and Wells, K. D. (1993). Culture of pig embryos. J. Reprod. Fertil. Suppl. 48, 61–73.
PubMed |

Petters, R. M. , Alexander, C. A. , Wells, K. D. , Collins, E. B. , and Sommer, J. R. , et al. (1997). Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa. Nat. Biotechnol. 15, 965–970.
CrossRef | PubMed |

Peura, T. T. (2003). Improved in vitro development rates of sheep somatic nuclear transfer embryos by using a reverse-order zona-free cloning method. Cloning Stem Cells 5, 13–24.
CrossRef | PubMed |

Phelps, C. J. , Koike, C. , Vaught, T. D. , Boone, J. , and Wells, K. D. , et al. (2003). Production of α-1,3-galatosyltransferase deficient pigs. Science 299, 411–414.
CrossRef | PubMed |

Polejaeva, I. A. , Chen, S. H. , Vaught, T. D. , Page, R. L. , and Mullins, J. , et al. (2000). Cloned pigs prduced by nuclear transfer from adult somatic cells. Nature 407, 86–90.
CrossRef | PubMed |

Polge, C. , Rowson, L. E. , and Chang, M. C. (1966). The effect of reducing the number of embryos during early stages of gestation on the maintenance of pregnancy in the pig. J. Reprod. Fertil. 12, 395–397.
PubMed |

Prather, R. S. , Sims, M. M. , and First, N. L. (1989). Nuclear transplantation in early pig embryos. Biol. Reprod. 41, 414–418.
CrossRef | PubMed |

Prather, R. S. , Sutovsky, P. , and Green, J. A. (2004). Nuclear remodeling and reprogramming in transgenic pig production. Exp. Biol. Med. 229, 1120–1126.


Ramsoondar, J. J. , Macháty, Z. , Costa, C. , Williams, B. , Fodor, W. L. , and Bondioli, K. R. (2003). Production of α-1,3-galactosyltransferase-knockout cloned pigs expressing human α-1,2-fucosylosyltransferase. Biol. Reprod. 69, 437–445.
CrossRef | PubMed |

Ravelingien, A. (2005). Use of pigs for xenotransplantation: the speciesism by proxy syndrome. Xenotransplantation 12, 235–239.
CrossRef | PubMed |

Ravelingien, A. , and Braeckman, J. (2004). To the core of porcine matter: evaluating arguments against producing transgenic pigs. Xenotransplantation 11, 371–375.
CrossRef | PubMed |

Ravelingien, A. , Mortier, F. , Mortier, E. , Keremans, I. , and Braeckman, J. (2004). Proceeding with clinical trials of animal to human organ transplantation: a way out of the dilemma. J. Med. Ethics 30, 92–98.
CrossRef | PubMed |

Rebellato, L. M. , Verbanac, K. M. , and Haisch, C. E. (2005). The current status of xenotransplantation. Curr. Surg. 62, 481–488.
CrossRef | PubMed |

Reemtsma, K. , Mc Cracken, B. H. , Schlegel, J. U. , and Pearl, M. (1964). Heterotransplantation of the kidney: two clinical experiences. Science 143, 700–702.
CrossRef | PubMed |

Renard, J. P. , Zhou, Q. , LeBourhis, D. , Chavatte-Palmer, P. , Hue, I. , Heyman, Y. , and Vignon, X. (2002). Nuclear transfer technologies: between successes and doubts. Theriogenology 57, 203–222.
CrossRef | PubMed |

Rhind, S. M. , Taylor, J. E. , De Sousa, P. A. , King, T. J. , McGarry, M. , and Wilmut, I. (2003). Human cloning: can it be made safe? Nat. Rev. Genet. 4, 855–864.
CrossRef | PubMed |

Ribas, R. , Oback, B. , Ritchie, W. , Chebotareva, T. , and Ferrier, P. , et al. (2005). Development of a zona-free method of nuclear transfer in the mouse. Cloning Stem Cells 7, 126–138.
CrossRef | PubMed |

Roh, S. , and Hwang, W. S. (2002). In vitro development of porcine parthenogenetic and cloned embryos: comparison of oocyte-activating techniques, various culture systems and nuclear transfer methods. Reprod. Fertil. Dev. 14, 93–99.
CrossRef | PubMed |

Sage, D. , Hassel, P. , Petersen, B. , Mysegades, W. , Westermann, P. , Lucas-Hahn, A. , and Niemann, H. (2005). Improved in vitro development of porcine embryos produced by nuclear transfer, IVF and parthenogenesis. Reprod. Fertil. Dev. 17, 181.
CrossRef |

Sauer, I. , Kardassis, D. , Zeillinger, K. , Pascher, A. , and Gruenwald, A. , et al. (2003). Clinical extracorporeal hybrid liver support – phase I study with primary porcine liver cells. Xenotransplantation 10, 460–469.
CrossRef | PubMed |

Schoevers, E. J. , Kidson, A. , Verheijden, J. H. , and Bevers, M. M. (2003). Effect of follicle-stimulating hormone on nuclear and cytoplasmic maturation of sow oocytes in vitro. Theriogenology 59, 2017–2028.
CrossRef | PubMed |

Schoevers, E. J. , Bevers, M. M. , Roelen, B. A. , and Colenbrander, B. (2005). Nuclear and cytoplasmic maturation of sow oocytes are not synchronized by specific meiotic inhibition with roscovitine during in vitro maturation. Theriogenology 63, 1111–1130.
CrossRef | PubMed |

Seveno, C. , Fellous, M. , Ashton-Chess, J. , Soulillou, J. P. , and Vanhove, B. (2005). On the acceptability of xenografts. Med. Sci. 21, 302–308.


Sheil, A. (2002). Xenogeneic bioartificial liver support: where are we now? Transplant. Proc. 34, 2493–2495.
CrossRef | PubMed |

Shin, M. R. , Park, S. W. , Shim, H. , and Kim, N. H. (2002). Nuclear and microtubule reorganization in nuclear-transferred bovine embryos. Mol. Reprod. Dev. 62, 74–82.
CrossRef | PubMed |

Siegel, J. B. , Grey, S. T. , Lesnikoski, B. A. , Kopp, C. W. , Soares, M. , Schulte am Esch, J. , Bach, F. H. , and Robson, S. C. (1997). Xenogeneic endothelial cells activate human prothrombin. Transplantation 64, 888–896.
CrossRef | PubMed |

Soulillou, J.-P. (2005). How and when will cardiac xenotransplantation enter the clinic. The recurrent debate has gained in realism. Nat. Clin. Pract. Cardiovasc. Med. 2, 550–551.
CrossRef | PubMed |

Stockmann, H. , and Ijzermans, J. (2002). Prospects for temporary treatment of acute liver failure. Eur. J. Gastroenterol. Hepatol. 14, 195–203.
CrossRef | PubMed |

Stowers, A. W. , Chen, L. H. , Zhang, Y. , Kennedy, M. C. , and Zou, L. , et al. (2002). A recombinant vaccine expressed in the milk of transgenic mice protects Aotus monkeys from a lethal challenge with Plasmodium falciparum. Proc. Natl Acad. Sci. USA 99, 339–344.
CrossRef | PubMed |

Sun, X. , Zhang, L. , Cheng, J. , Li, S. , Wang, Q. , Wei, Q. , Zeng, Y. , Zeng, R. , and Li, Y. (2004a). Study of renal function matching between Banna Minipig Inbred line and human. Transplant. Proc. 36, 2488–2489.
CrossRef | PubMed |

Sun, X. , Zhang, L. , Cheng, J. , Wang, L. , Wei, Q. , Li, S. , Zeng, R. , Zeng, Y. , and Li, Y. (2004b). Study of hepatic function matching between Banna Minipig Inbred and humans. Transplant. Proc. 36, 2492–2494.
CrossRef | PubMed |

Suzuki, C. , Iwamura, S. , and Yoshioka, K. (2004). Birth of piglets through the non-surgical transfer of blastocysts produced in vitro. J. Reprod. Dev. 50, 487–491.
CrossRef | PubMed |

Swain, J. E. , Bormann, C. L. , and Krisher, R. L. (2001). Development and viability of in vitro derived porcine blastocysts cultured in NCSU23 and G1.2/G2.2 sequential medium. Theriogenology 56, 459–469.
CrossRef | PubMed |

Swanson K., Kuzmuk K., Meyers S., Beever J., Adams S., et al. (2005). Swine in biomedical research. In ‘Proceedings of the Swine in Biomedical Research Conference’, 27–29 January 2005, Chicago, IL. pp. 42–43.

Switzer, W. M. , Michler, R. E. , Shanmugan, V. , Matthews, A. , and Hussain, A. I. , et al. (2001). Lack of cross-species transmission of porcine endogenous retrovirus infection to nonhuman primate recipients of porcine cells, tissues and organs. Transplantation 71, 959–965.
CrossRef | PubMed |

Taka, M. , Iwayama, H. , and Fukui, Y. (2005). Effect of the well of the well (WOW) system on in vitro culture for porcine embryos after intracytoplasmic sperm injection. J. Reprod. Dev. 51, 533–537.
CrossRef | PubMed |

Takahagi, Y. , Fujimura, T. , Miyagawa, S. , Nagashima, H. , Shigehisa, T. , Shirakura, R. , and Murakami, H. (2005). Production of alpha-1,3-galactosyltransferase gene knockout pigs expressing both human decay-accelerating factor and N-acetylglucosaminyltransferase III. Mol. Reprod. Dev. 71, 331–338.
CrossRef | PubMed |

Takeda, K. , Tasai, M. , Iwamoto, M. , Akita, T. , Tagami, T. , Nirasawa, K. , Hanada, H. , and Onishi, A. (2006). Transmission of mitochondrial DNA in pigs and progeny derived from nuclear transfer of Meishan pig fibroblast cells. Mol. Reprod. Dev. 73, 306–312.
CrossRef | PubMed |

Tani, T. , Kato, Y. , and Tsunoda, Y. (2001). Direct exposure of chromosomes to nonactivated ovum cytoplasm is effective for bovine somatic cell nucleus reprogramming. Biol. Reprod. 64, 324–330.
CrossRef | PubMed |

Tatemoto, H. , Muto, N. , Sunagawa, I. , Shinjo, A. , and Nakada, T. (2004). Protection of porcine oocytes against cell damage caused by oxidative stress during in vitro maturation: role of superoxide dismutase activity in porcine follicular fluid. Biol. Reprod. 71, 1150–1157.
CrossRef | PubMed |

Tearle, R. G. , Tange, M. J. , Zannettino, Z. L. , Katerelos, M. , and Shinkel, T. A. , et al. (1996). The alpha-1,3-galactosyltransferase knockout mouse. Implications for xenotransplantation. Transplantation 61, 13–19.
CrossRef | PubMed |

Tecirlioglu, R. T. , French, A. J. , Lewis, I. M. , Vajta, G. , Korfiatis, N. A. , Hall, V. J. , Ruddock, N. T. , Cooney, M. A. , and Trounson, A. O. (2004). Birth of a cloned calf derived from a vitrified hand-made cloned embryo. Reprod. Fertil. Dev. 15, 361–366.
CrossRef | PubMed |

Tellides, G. , Tereb, D. A. , Kirkiles-smith, N. C. , Kim, R. , Wilson, J. H. , Schechner, J. S. , Lorber, M. I. , and Pober, J. S. (2000). Interferon-γ elicits arteriosclerosis in the absence of leukocytes. Nature 403, 207–211.
CrossRef | PubMed |

Theuring, F. , Thunecke, M. , Kosciessa, U. , and Turner, J. D. (1997). Transgenic animals as models of neurodegenerative diseases in humans. Trends Biotechnol. 15, 320–325.
CrossRef | PubMed |

Thibier, M. (2004). Stabilization of numbers of in vivo collected embryos in cattle but significant increases of in vitro produced bovine embryos in some parts of the world. Data Retrieval Committee Annual Reports. IETS Newsletter 22, 12–19.


Thouas, G. A. , Jones, G. M. , and Trounson, A. O. (2003). The ‘GO’ system–a novel method of microculture for in vitro development of mouse zygotes to the blastocyst stage. Reproduction 126, 161–169.
CrossRef | PubMed |

Tomii, R. , Kurome, M. , Ochiai, T. , Wako, N. , Ueda, H. , Hirakawa, K. , Kano, K. , and Nagashima, H. (2005). Production of cloned pigs by nuclear transfer of preadipocytes established from adult mature adipocytes. Cloning Stem Cells 7, 279–288.
PubMed |

Tong, G. Q. , Heng, B. C. , Chen, N. Q. , Yip, W. Y. , and Ng, S. C. (2004). Effects of elevated temperature in vivo on the maturational and developmental competence of porcine germinal vesicle stage oocytes. J. Anim. Sci. 82, 3175–3180.
PubMed |

Toyokawa, K. , Harayama, H. , and Miyake, M. (2005). Exogenous hyaluronic acid enhances porcine parthenogenetic embryo development in vitro possibly mediated by CD44. Theriogenology 64, 378–392.
CrossRef | PubMed |

Triller, K. , and Bobinski, M. A. (2004). Tort liability of xenotransplantation centers. Xenotransplantation 11, 310–314.
CrossRef | PubMed |

Tseng, Y. L. , Kuwaki, K. , Dor, F. , Shimizu, A. , and Houser, S. , et al. (2005). Alpha-1,3-galactosyltransferase gene-knockout pig heart transplantation in baboons with survival approaching 6 months. Transplantation 80, 1493–1500.
CrossRef | PubMed |

Tunquist, B. J. , and Maller, J. L. (2003). Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs. Genes Dev. 17, 683–710.
CrossRef | PubMed |

Vajta, G. , Peura, T. T. , Holm, P. , Paldi, A. , Greve, T. , Trounson, A. O. , and Callesen, H. (2000). New method for culture of zona-included or zona-free embryos: the Well of the Well (WOW) system. Mol. Reprod. Dev. 55, 256–264.
CrossRef | PubMed |

Vajta, G. , Lewis, I. M. , Hyttel, P. , Thouas, G. A. , and Trounson, A. O. (2001). Somatic cell cloning without micromanipulators. Cloning 3, 89–95.
CrossRef | PubMed |

Vajta, G. , Lewis, I. M. , Trounson, A. O. , Purup, S. , Maddox-Hyttel, P. , Schmidt, M. , Pedersen, H. G. , Greve, T. , and Callesen, H. (2003). Handmade somatic cell cloning in cattle: analysis of factors contributing to high efficiency in vitro. Biol. Reprod. 68, 571–578.
CrossRef | PubMed |

Vajta, G. , Bartels, P. , Joubert, J. , de la Rey, M. , Treadwell, R. , and Callesen, H. (2004). Production of a healthy calf by somatic cell nuclear transfer without micromanipulators and carbon dioxide incubators using the handmade cloning (HMC) and the submarine incubation system (SIS). Theriogenology 62, 1465–1472.
CrossRef | PubMed |

Vajta, G. , Kragh, P. M. , Mtango, N. R. , and Callesen, H. (2005). Handmade cloning approach: potentials and limitations. Reprod. Fertil. Dev. 17, 97–112.
CrossRef | PubMed |

van de Kerkhove, M. P. , Poyck, P. P. , Deurholt, T. , Hoekstra, R. , Chamuleau, R. A. , and van Gulik, T. M. (2005a). Liver support therapy: an overview of the AMC-bioartificial liver research. Dig. Surg. 22, 254–264.
CrossRef | PubMed |

van de Kerkhove, M. P. , Germans, M. R. , Deurholt, T. , Hoekstra, R. , Joziasse, D. H. , van Wijk, A. C. , van Gulik, T. M. , Chamuleau, R. A. , and Roos, A. (2005b). Evidence for Galα(1–3)Gal expression on primary porcine hepatocytes: implications for bioartificial liver systems. J. Hepatol. 42, 541–547.
CrossRef | PubMed |

Verma, P. J. , Du, Z. T. , Crocker, L. , Faast, R. , Grupen, C. G. , McIlfatrick, S. M. , Ashman, R. J. , Lyons, I. G. , and Nottle, M. B. (2000). In vitro development of porcine nuclear transfer embryos constructed using fetal fibroblasts. Mol. Reprod. Dev. 57, 262–269.
CrossRef | PubMed |

Vodička, P. , Smetana, K. , Dvořanková, B. , Emerick, T. , Xu, Y. Z. , Ourednik, J. , Ourednik, V. , and Motlík, J. (2005). The miniature pig as an animal model in biomedical research. Ann. N. Y. Acad. Sci. 1049, 161–171.
CrossRef | PubMed |

Walker, S. C. , Shin, T. , Zaunbrecher, G. M. , Romano, J. E. , Johnson, G. A. , Bazer, F. W. , and Piedrahita, J. A. (2002). A highly efficient method for porcine cloning by nuclear transfer using in vitro-matured oocytes. Cloning Stem Cells 4, 105–112.
CrossRef | PubMed |

Watanabe, S. , Iwamoto, M. , Suzuki, S. , Fuchimoto, D. , Honma, D. , Nagai, T. , Hashimoto, M. , Yazaki, S. , Sato, M. , and Onishi, A. (2005). A novel method for the production of transgenic cloned pigs: electroporation-mediated gene transfer to non-cultured cells and subsequent selection with puromycin. Biol. Reprod. 72, 309–315.
CrossRef | PubMed |

Waterworth, P. D. , Cozzi, E. , Tolan, M. J. , Langford, G. , Braidley, P. , Chavez, G. , Dunning, J. , Wallwork, J. , and White, D. (1997). Pig-to-primate cardiac xenotransplantation and cyclophosphamide therapy. Transplant. Proc. 29, 899–900.
CrossRef | PubMed |

Weiss, R. A. (1998). Science, medicine, and the future: Xenotransplantation. BMJ 317, 931–934.
PubMed |

Wernersson R., Shierup M. H., Jørgensen F. G., Gorodkin J., Panitz F., et al. (2005). Pigs in sequence space: a 0.66x coverage Sino-Danish pig genome survey. In ‘Proceedings of the Swine in Biomedical Research Conference’, 27–29 January 2005, Chicago, IL. p. 27.

Wheeler, M. B. , Clark, S. G. , and Beebe, D. J. (2004). Developments in in vitro technologies for swine embryo production. Reprod. Fertil. Dev. 16, 15–25.
CrossRef | PubMed |

Whitaker, M. (2006). Calcium at fertilization and in early development. Physiol. Rev. 86, 25–88.
CrossRef | PubMed |

Wilmut, I. , Schnieke, A. E. , McWhir, J. , Kind, A. J. , and Campbell, K. H. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810–813.
CrossRef | PubMed |

Wilmut, I. , Beaujean, N. , de Sousa, P. A. , Dinnyes, A. , King, T. J. , Paterson, L. A. , Wells, D. N. , and Young, L. E. (2002). Somatic cell nuclear transfer. Nature 419, 583–586.
CrossRef | PubMed |

Wongsrikeao, P. , Otoi, T. , Karja, N. W. , Agung, B. , Nii, M. , and Nagai, T. (2005). Effects of ovary storage time and temperature on DNA fragmentation and development of porcine oocytes. J. Reprod. Dev. 51, 87–97.
CrossRef | PubMed |

Wongsrikeao, P. , Otoi, T. , Yamasaki, H. , Agung, B. , Taniguchi, M. , Naoi, H. , Shimizu, R. , and Nagai, T. (2006). Effects of single and double exposure to brilliant cresyl blue on the selection of porcine oocytes for in vitro production of embryos. Theriogenology 66, 366–372.
CrossRef | PubMed |

Wu, G. M. , Lai, L. , Mao, J. , McCauley, T. C. , and Caamano, J. N. , et al. (2004). Birth of piglets by in vitro fertilization of zona-free porcine oocytes. Theriogenology 62, 1544–1556.
CrossRef | PubMed |

Yamada, K. , Yazawa, K. , Shimizu, A. , Iwanaga, T. , and Hisashi, Y. , et al. (2005). Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha-1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat. Med. 11, 32–34.
CrossRef | PubMed |

Yang, Y. G. , Wood, J. C. , Lan, P. , Wilkinson, R. A. , Sykes, M. , Fishman, J. A. , and Patience, C. (2004). Mouse retrovirus mediates porcine endogenous retrovirus transmission into human cells in long-term human-porcine chimeric mice. J. Clin. Invest. 114, 695–700.
CrossRef | PubMed |

Yin, X. J. , Tani, T. , Yonemura, I. , Kawakami, M. , Miyamoto, K. , Hasegawa, R. , Kato, Y. , and Tsunoda, Y. (2002). Production of cloned pigs from adult somatic cells by chemically assisted removal of maternal chromosomes. Biol. Reprod. 67, 442–446.
CrossRef | PubMed |

Yin, X.J. , Cho, S.K. , Park, M.R. , Im, Y.J. , and Park, J.J. , et al. (2003). Nuclear remodelling and the developmental potential of nuclear transferred porcine oocytes under delayed-activated conditions. Zygote 11, 167–174.
CrossRef | PubMed |

Yoneda, A. , Suzuki, K. , Mori, T. , Ueda, J. , and Watanabe, T. (2004). Effects of delipidation and oxygen concentration on in vitro development of porcine embryos. J. Reprod. Dev. 50, 287–295.
CrossRef | PubMed |

Yoon, K. W. , Shin, T. Y. , Park, J. I. , Roh, S. , Lim, J. M. , Lee, B. C. , Hwang, W. S. , and Lee, E. S. (2000). Development of porcine oocytes from preovulatory follicles of different sizes after maturation in media supplemented with follicular fluids. Reprod. Fertil. Dev. 12, 133–139.
CrossRef | PubMed |

Yoshioka, K. , Suzuki, C. , Tanaka, A. , Anas, I. M. , and Iwamura, S. (2002). Birth of piglets derived from porcine zygotes cultured in a chemically defined medium. Biol. Reprod. 66, 112–119.
CrossRef | PubMed |

Young, L. E. , Sinclair, K. D. , and Wilmut, I. (1998). Large offspring syndrome in cattle and sheep. Rev. Reprod. 3, 155–163.
CrossRef | PubMed |

Zhang, L. , Li, Y. , Liu, J. , Zeng, Y. , Zeng, R. , and Cheng, J. (2004). Activation of human coagulation system by liver-derived clotting factors of Banna Minipig Inbred line. Transplant. Proc. 36, 2490–2491.
CrossRef | PubMed |

Zhang, L. , Li, Y. , Jiang, H. , Liu, J. , Zeng, Y. , and Cheng, J. (2005). Comparison of hepatic coagulant, fibrinolytic, and anticoagulant functions between Banna Minipig Inbred line and humans. Transplantation 79, 1128–1131.
CrossRef | PubMed |

Zhang, Y.H. , Pan, D.K. , Sun, X.Z. , Sun, G.J. , Wang, X.B. , Liu, X.H. , Li, Y. , Dai, Y.P. , and Li, N. (2006). Production of porcine cloned transgenic embryos expressing green fluorescent protein by somatic cell nuclear transfer. Sci. China Ser. C Sci. 49, 164.
CrossRef |

Zhu, M. , Wang, S. S. , Xia, Z. X. , Cao, R. H. , Chen, D. , Huang, Y. B. , Liu, B. , Chen, Z. K. , and Chen, S. (2005). Inhibition of xenogeneic response in porcine endothelium using RNA interference. Transplantation 79, 289–296.
CrossRef | PubMed |



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