Journal of Embryo Transfer (한국수정란이식학회지)

The Korean Society of Embryo Transfer (한국수정란이식학회)
권호 표지
DOI QR코드

DOI QR Code

Production of Transgenic Micro-Pig Expressing Human Heme Oxygenase 1

  • Koo, Ok Jae (Laboratory Animal Research Center, Samsung Biomedical Research Institute) ;
  • Oh, Hyun Ju (Dept. of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University) ;
  • Lee, Byeong Chun (Dept. of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University)
  • Received : 2015.12.21
  • Accepted : 2015.12.29
  • Published : 2015.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Xenotransplantation of pig islet regarded as a good alternative to allotransplantation. However, cellular death mediated by hypoxia-reoxygenation injury after transplantation disturb success of this technique. In the present study, we produce transgenic pig expressing human heme oxygenase 1 (HO1) genes to overcome cellular death for improving efficiency of islet xenotransplantation. Particularly, Korean miniature pig breed, Micro-Pig, was used in the present study. Somatic cell nuclear transfer (SCNT) technique was used to produce the HO1 transgenic pig. Six alive transgenic piglets were produced and all the transgenic pigs were founded to have transgene in their genomic DNA and the gene was expressed in all tested organs. Also, in vitro cultured fibroblasts derived from the HO1 transgenic pig showed low reactive oxygen species level, improved cell viability and reduced apoptosis level.

Keywords

References

  1. Alessenko AV, Boikov P, Filippova GN, Khrenov AV, Loginov AS and Makarieva ED. 1997. Mechanisms of cycloheximide-induced apoptosis in liver cells. FEBS. Lett. 416:113-116. https://doi.org/10.1016/S0014-5793(97)01161-7
  2. Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F, Eaton JW and Vercellotti GM. 1992. Ferritin: A cytoprotective antioxidant strategem of endothelium. J. Biol. Chem. 267:18148-18153.
  3. Biarnes M, Montolio M, Nacher V, Raurell M, Soler J and Montanya E. 2002. Beta-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia. Diabetes. 51:66-72. https://doi.org/10.2337/diabetes.51.1.66
  4. Bonner-Weir S and Orci L. 1982. New perspectives on the microvasculature of the islets of Langerhans in the rat. Diabetes. 31:883-889. https://doi.org/10.2337/diab.31.10.883
  5. Braudeau C, Bouchet D, Toquet C, Tesson L, Menoret S, Iyer S, Laboisse C, Willis D, Jarry A, Buelow R, Anegon I and Chauveau C. 2003. Generation of heme oxygenase-1-transgenic rats. Exp. Biol. Med. (Maywood) 228:466-471. https://doi.org/10.1177/15353702-0322805-07
  6. Cardona K, Korbutt GS, Milas Z, Lyon J, Cano J, Jiang W, Bello-Laborn H, Hacquoil B, Strobert E, Gangappa S, Weber CJ, Pearson TC, Rajotte RV and Larsen CP. 2006. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat. Med. 12:304-306. https://doi.org/10.1038/nm1375
  7. Carlsson PO, Liss P, Andersson A and Jansson L. 1998. Measurements of oxygen tension in native and transplanted rat pancreatic islets. Diabetes. 47:1027-1032. https://doi.org/10.2337/diabetes.47.7.1027
  8. Chen XB, Li YX, Jiao Y, Dong WP, Li G, Chen J and Tan JM. 2007. Influence of heme oxygenase-1 gene transfer on the viability and function of rat islets in in vitro culture. World J. Gastroenterol. 13:1053-1059. https://doi.org/10.3748/wjg.v13.i7.1053
  9. Cooper DK, Gollackner B, Knosalla C and Teranishi K. 2002. Xenotransplantation-how far have we come? Transpl. Immunol. 9:251-256. https://doi.org/10.1016/S0966-3274(02)00010-2
  10. d'Apice AJ and Cowan PJ. 2008a. Gene-modified pigs. Xenotransplantation 15:87-90. https://doi.org/10.1111/j.1399-3089.2008.00457.x
  11. d'Apice AJ and Cowan PJ. 2008b. Xenotransplantation: The next generation of engineered animals. Transpl. Immunol. 21:111-5.
  12. Emamaullee J, Liston P, Korneluk RG, Shapiro AM and Elliott JF. 2005. XIAP overexpression in islet beta-cells enhances engraftment and minimizes hypoxia-reperfusion injury. Am. J. Transplant. 5:1297-1305. https://doi.org/10.1111/j.1600-6143.2005.00891.x
  13. Evans JL, Goldfine ID, Maddux BA and Grodsky GM. 2003. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes. 52:1-8. https://doi.org/10.2337/diabetes.52.1.1
  14. Gardner AM, Xu FH, Fady C, Jacoby FJ, Duffey DC, Tu Y and Lichtenstein A. 1997. Apoptotic vs. nonapoptotic cytotoxicity induced by hydrogen peroxide. Free. Radic. Biol. Med. 22:73-83. https://doi.org/10.1016/S0891-5849(96)00235-3
  15. Gossett R, Kier AB, Schroeder F, McConkey D, Fadok V and Amoss MS, Jr. 1996. Cycloheximide-induced apoptosis in melanoma cells derived from regressing cutaneous tumours of Sinclair swine. J. Comp. Pathol. 115:353-372. https://doi.org/10.1016/S0021-9975(96)80071-5
  16. Hering BJ, Wijkstrom M, Graham ml, Hardstedt M, Aasheim TC, Jie T, Ansite JD, Nakano M, Cheng J, Li W, Moran K, Christians U, Finnegan C, Mills CD, Sutherland DE, Bansal-Pakala P, Murtaugh MP, Kirchhof N and Schuurman HJ. 2006. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat. Med. 12:301-303. https://doi.org/10.1038/nm1369
  17. Katori M, Busuttil RW and Kupiec-Weglinski JW. 2002. Heme oxygenase-1 system in organ transplantation. Transplantation 74:905-912. https://doi.org/10.1097/00007890-200210150-00001
  18. Koo OJ, Jang G, Kwon DK, Kang JT, Kwon OS, Park HJ, Kang SK and Lee BC. 2008. Electrical activation induces reactive oxygen species in porcine embryos. Theriogenology 70:1111-1118. https://doi.org/10.1016/j.theriogenology.2008.06.031
  19. Laumonier T, Yang S, Konig S, Chauveau C, Anegon I, Hoffmeyer P and Menetrey J. 2008. Lentivirus mediated HO-1 gene transfer enhances myogenic precursor cell survival after autologous transplantation in pig. Mol. Ther. 16:404-410. https://doi.org/10.1038/sj.mt.6300354
  20. Lepore DA, Shinkel TA, Fisicaro N, Mysore TB, Johnson LE, d'Apice AJ and Cowan PJ. 2004. Enhanced expression of glutathione peroxidase protects islet beta cells from hypoxiareoxygenation. Xenotransplantation 11:53-59. https://doi.org/10.1111/j.1399-3089.2004.00082.x
  21. Li C and Jackson RM. 2002. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am. J. Physiol. Cell. Physiol. 282:C227-241. https://doi.org/10.1152/ajpcell.00112.2001
  22. Li YX, Li G, Dong WP, Lu DR and Tan JM. 2006. Protection of human islets from induction of apoptosis and improved islet function with HO-1 gene transduction. Chin. Med. J. (Engl) 119:1639-1645.
  23. Maines MD. 1997. The heme oxygenase system: a regulator of second messenger gases. Annu. Rev. Pharmacol. Toxicol. 37:517-554. https://doi.org/10.1146/annurev.pharmtox.37.1.517
  24. Maines MD. 2002. Heme oxygenase 1 transgenic mice as a model to study neuroprotection. Methods Enzymol. 353:374-388. https://doi.org/10.1016/S0076-6879(02)53062-7
  25. Mysore TB, Shinkel TA, Collins J, Salvaris EJ, Fisicaro N, Murray-Segal LJ, Johnson LE, Lepore DA, Walters SN, Stokes R, Chandra AP, O'Connell PJ, d'Apice AJ and Cowan PJ. 2005. Overexpression of glutathione peroxidase with two isoforms of superoxide dismutase protects mouse islets from oxidative injury and improves islet graft function. Diabetes. 54:2109-2116. https://doi.org/10.2337/diabetes.54.7.2109
  26. Parr EL, Bowen KM and Lafferty KJ. 1980. Cellular changes in cultured mouse thyroid glands and islets of Langerhans. Transplantation 30:135-141. https://doi.org/10.1097/00007890-198008000-00012
  27. Petrache I, Otterbein LE, Alam J, Wiegand GW and Choi AM. 2000. Heme oxygenase-1 inhibits TNF-alpha-induced apoptosis in cultured fibroblasts. Am. J. Physiol. Lung. Cell Mol. Physiol. 278:L312-319. https://doi.org/10.1152/ajplung.2000.278.2.L312
  28. Pileggi A, Molano RD, Berney T, Cattan P, Vizzardelli C, Oliver R, Fraker C, Ricordi C, Pastori RL, Bach FH and Inverardi L. 2001. Heme oxygenase-1 induction in islet cells results in protection from apoptosis and improved in vivo function after transplantation. Diabetes. 50:1983-1991. https://doi.org/10.2337/diabetes.50.9.1983
  29. Rood PP, Buhler LH, Bottino R, Trucco M and Cooper DK. 2006. Pig-to-nonhuman primate islet xenotransplantation: A review of current problems. Cell Transplant. 15:89-104. https://doi.org/10.3727/000000006783982052
  30. Stocker R. 1990. Induction of haem oxygenase as a defence against oxidative stress. Free. Radic. Res. Commun. 9:101-112. https://doi.org/10.3109/10715769009148577
  31. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN and Ames BN. 1987. Bilirubin is an antioxidant of possible physiological importance. Science 235:1043-1046. https://doi.org/10.1126/science.3029864
  32. Suzuki C, Yoshioka K, Sakatani M and Takahashi M. 2007. Glutamine and hypotaurine improves intracellular oxidative status and in vitro development of porcine preimplantation embryos. Zygote 15:317-324. https://doi.org/10.1017/S0967199407004273
  33. Tiedge M, Lortz S, Drinkgern J and Lenzen S. 1997. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes. 46:1733-1742. https://doi.org/10.2337/diab.46.11.1733
  34. Willis D, Moore AR, Frederick R and Willoughby DA. 1996. Heme oxygenase: A novel target for the modulation of the inflammatory response. Nat. Med. 2:87-90. https://doi.org/10.1038/nm0196-87
  35. Yeom HJ, Koo OJ, Yang J, Cho B, Hwang JI, Park SJ, Hurh S, Kim H, Lee EM, Ro H, Kang JT, Kim SJ, Won JK, O'Connell PJ, Kim H, Surh CD, Lee BC and Ahn C. 2012. Generation and characterization of human heme oxygenase-1 transgenic pigs. PLoS. One 7:e46646. https://doi.org/10.1371/journal.pone.0046646
  36. Zhen-Wei X, Jian-Le S, Qi Q, Wen-Wei Z, Xue-Hong Z and Zi-Li Z. 2007. Heme oxygenase-1 improves the survival of discordant cardiac xenograft through its anti-inflammatory and anti-apoptotic effects. Pediatr. Transplant. 11:850-859. https://doi.org/10.1111/j.1399-3046.2007.00701.x