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Production and Breeding of Transgenic Cloned Pigs Expressing Human CD73

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초록

One of the reasons to causing blood coagulation in the tissue of xenografted organs was known to incompati-bility of the blood coagulation and anti-coagulation regulatory system between TG pigs and primates. Thus, overexpression of human CD73 (hCD73) in the pig endothelial cells is considered as a method to reduce coagulopathy after pig-to-non-human-primate xenotransplantation. This study was performed to produce and breed transgenic pigs expressing hCD73 for the studies immune rejection responses and could provide a successful application of xenotransplantation. The transgenic cells were con-structed an hCD73 expression vector under control porcine Icam2 promoter (pIcam2-hCD73) and established donor cell lines expressing hCD73. The numbers of transferred reconstructed embryos were 127 ± 18.9. The pregnancy and delivery rate of surrogates were 8/18 (44%) and 3/18 (16%). The total number of delivered cloned pigs were 10 (2 alive, 7 mummy, and 1 died after birth). Among them, three live hCD73-pigs were successfully delivered by Caesarean section, but one was dead af-ter birth. The two hCD73 TG cloned pigs had normal reproductive ability. They mated with wild type (WT) MGH (Massachu-setts General Hospital) female sows and produced totally 16 piglets. Among them, 5 piglets were identified as hCD73 TG pigs. In conclusion, we successfully generated the hCD73 transgenic cloned pigs and produced their litters by natural mating. It can be possible to use a mate for the production of multiple transgenic pigs such as α-1,3-galactosyltransferase knock-out /hCD46 for xenotransplantation.

Abstract

One of the reasons to causing blood coagulation in the tissue of xenografted organs was known to incompati-bility of the blood coagulation and anti-coagulation regulatory system between TG pigs and primates. Thus, overexpression of human CD73 (hCD73) in the pig endothelial cells is considered as a method to reduce coagulopathy after pig-to-non-human-primate xenotransplantation. This study was performed to produce and breed transgenic pigs expressing hCD73 for the studies immune rejection responses and could provide a successful application of xenotransplantation. The transgenic cells were con-structed an hCD73 expression vector under control porcine Icam2 promoter (pIcam2-hCD73) and established donor cell lines expressing hCD73. The numbers of transferred reconstructed embryos were 127 ± 18.9. The pregnancy and delivery rate of surrogates were 8/18 (44%) and 3/18 (16%). The total number of delivered cloned pigs were 10 (2 alive, 7 mummy, and 1 died after birth). Among them, three live hCD73-pigs were successfully delivered by Caesarean section, but one was dead af-ter birth. The two hCD73 TG cloned pigs had normal reproductive ability. They mated with wild type (WT) MGH (Massachu-setts General Hospital) female sows and produced totally 16 piglets. Among them, 5 piglets were identified as hCD73 TG pigs. In conclusion, we successfully generated the hCD73 transgenic cloned pigs and produced their litters by natural mating. It can be possible to use a mate for the production of multiple transgenic pigs such as α-1,3-galactosyltransferase knock-out /hCD46 for xenotransplantation.

참고문헌 (38)

  1. Arulkumaran N, "Purinergic signaling in inflammato-ry renal disease", Front Physiol, 4, pp.1~7 (2013)
  2. Bauerle JD, "Adenosine generation and signaling during acute kid-ney injury", J. Am. Soc. Nephrol, 22, pp.14~20 (2011)
  3. Chen G, "Acute rejection is asso-ciated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys", Nat Med, 11, pp.1295~1298 (2005)
  4. Choi K, "Production of heterozygous alpha 1,3-galactosyltransferase (GGTA1) knock-out transgenic miniature pigs expressing human CD39", Transgenic Res, 26, pp.209~224 (2017)
  5. Cooper DK, "Clinical lung xeno-transplantation-- what donor genetic modifications may be necessary?", Xenotransplantation, 19, pp.144~158 (2012)
  6. Cowan PJ, "Complement activation and coagulation in xenotransplantation", Immunol Cell Biol, 87, pp.203~208 (2009)
  7. Cowan PJ, "Coagulation and the xenograft endothe-lium", Xenotransplantation, 14, pp.7~12 (2007)
  8. Crikis S, "Intravascular throm-bosis in discordant xenotransplantation", Transplanta-tion, 82, pp.1119~1123 (2006)
  9. Daval JL, "Physiological and pharmacological properties of adenosine: therapeutic implications", Life Sci, 49, pp.1435~1453 (1991)
  10. Delikouras A, "Endothelial cell cytoprotection in-duced in vitro by allo- or xenoreactive antibodies is mediated by signaling through adenosine A2 receptors", Eur J Immunol, 33, pp.3127~3135 (2003)
  11. Ekser B, "Clin-ical xenotransplantation: the next medical revolution?", Lancet, 379, pp.672~683 (2012)
  12. Fujimura T, "Production of alpha 1,3-galactosyltransferase gene-deficient pigs by somatic cell nuclear transfer: a novel selection method for gal alpha 1,3-Gal antigen-deficient cells", Mol Reprod Dev, 75, pp.1372~1378 (2008)
  13. Higginbotham L, "Long-term survival of pig-to-primate renal xenotransplant using costimulation-blockade immuno-suppression", Transplantation, pp.s72~s73 (2015)
  14. Houser SL, "Thrombotic microangiopathy and graft arteriopathy in pig hearts following transplantation into baboons", Xenotransplantation, 11, pp.416~425 (2004)
  15. 황인설, "Production of Cloned Korean Native Pig by Somatic Cell Nuclear Transfer", 발생과 생식, 19(2), pp.79~84 (2015), 한국발생생물학회
  16. Iwase H, "Pig kidney graft survival in a baboon for 136 days: longest lifesupporting organ graft survival to date", Xenotrans-plantation, 22, pp.302~309 (2015)
  17. Khalpey Z, "Loss of ecto-50 nucleotidase from porcine en-dothelial cells after exposure to human blood: implica-tions for xenotransplantation", Biochim Biophys Acta, 1741, pp.191~198 (2005)
  18. Kim H, "Outcomes of alpha 1,3-GT-knockout porcine heart transplants into a preclinical nonhuman primate model", Transplant Proc, 45, pp.3085~3091 (2013)
  19. Kolber-Simonds D, "Production of alpha-1,3-galactosyl-transferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations", Proc Natl Acad Sci USA, 101, pp.7335~7340 (2004)
  20. Kuwaki K, "Heart transplantation in baboons using alpha 1, 3-galactosyltransferase gene-knockout pigs as donors: initial experience", Nat Med, 11, pp.29~31 (2005)
  21. Kwon DJ, "Generation of α-1,3-galactosyltransferase knocked-out transgenic cloned pigs with knocked-in five human genes", Transgenic Res, 26, pp.153~163 (2017)
  22. Lambrigts D, "Discordant organ xenotransplantation in primates: world experi-ence and current status", Transplantation, 66, pp.547~561 (1998)
  23. Lee HJ, "Characterization of transgenic pigs that express human decay accelerating factor and cell membrane-tethered human tissue factor pathway inhibitor", Reprod Domest Anim, 46, pp.325~332 (2011)
  24. Li P, "Biallelic knockout of the alpha-1,3 galactosyltransferase gene in porcine liver-derived cells using zinc finger nucleases", J Surg Res, 181, pp.e39~e45 (2013)
  25. Lin CC, "Coagulation dysre-gulation as a barrier to xenotransplantation in the pri-mate", Transpl Immunol, 21, pp.75~80 (2009)
  26. Lin CC, "Recipient tissue factor expres-sion is associated with consumptive coagulopathy in pig-to-primate kidney xenotransplantation", Am J Trans-plant, 10, pp.1556~1568 (2010)
  27. McGregor CG, "Cardiac xenotransplantation: progress toward the clinic", Transplantation, 78, pp.1569~1575 (2004)
  28. Mohiuddin MM, "Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardi-ac xenograft", Nat Commun, 7, pp.1~10 (2016)
  29. Nottle MB, "Production of homozygous alpha-1,3-galactosyltransferase knockout pigs by breeding and somatic cell nuclear transfer", Xenotransplantation, 14, pp.339~344 (2007)
  30. 오건봉, "돼지 혈관내피세포 특이적 CD73 발현 벡터가 도입된 돼지 섬유아세포생산", 한국수정란이식학회지, 31(3), pp.161~168 (2016), 한국수정란이식학회
  31. Phelps CJ, "Produc-tion of alpha 1,3-galactosyltransferase-deficient pigs", Science, 299, pp.411~414 (2003)
  32. Rocha PN, "Effector mechanisms in transplant rejection", Immunol Rev, 196, pp.51~64 (2003)
  33. Shimizu A, "Thrombotic microangiopathy associated with humoral rejection of cardiac xenografts from alpha1,3-galactosyltransferase gene-knockout pigs in baboons", Am J Pathol, 172, pp.1471~1481 (2008)
  34. Sitkovsky MV, "Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors", Annu Rev Immunol, 22, pp.657~682 (2004)
  35. Tseng YL, "alpha 1,3-Galactosyltransferase gene-knockout pig heart trans-plantation in baboons with survival approaching 6 months", Transplantation, 80, pp.1493~1500 (2005)
  36. Wheeler DG, "Transgenic swine: expression of human CD39 protects against myocardial injury", J Mol Cell Cardiol, 52, pp.958~961 (2012)
  37. Zhang B, "Platelet aggregation and thrombosis in xenotransplantation between pigs and humans", Thromb Res, 121, pp.433~441 (2008)
  38. Zimmermann H, "Extracellular purine metabolism", Drug Dev Res, 39, pp.337~352 (1996)

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