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The Minipig as an Animal Model in Biomedical Stem Cell Research

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Sourcebook of Models for Biomedical Research

Abstract

Pigs and miniature pigs are steadily gaining importance as large animal models in the field of regenerative medicine, including stem cell research. With their size, organ capacity, and physiology resembling in several aspects that of humans, pigs are well suited for preclinical experiments and long-term safety studies. In this chapter, we summarize our experience with the isolation and culture of several somatic stem cell populations from fetal and adult pig tissue and briefly review their potential usefulness in future stem cell-based therapies. We also provide protocols for the isolation of fetal porcine neural stem cells (NSCs), adult bone marrow mesenchymal stem cells (MSCs), and epidermal progenitor cells (EPCs) from adult hair follicles.

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References

  1. Kolber-Simonds D, Lai L, Watt SR, Denaro M, Arn S, Augenstein ML, et al. Production of alpha 1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations. Proc Natl Acad Sci USA 2004;101:7335–7340.

    Article  PubMed  CAS  Google Scholar 

  2. Tseng YL, Kuwaki K, Dor FJ, Shimizu A, Houser S, Hisashi Y, et al. alpha1,3-Galactosyltransferase gene-knockout pig heart transplantation in baboons with survival approaching 6 months. Transplantation 2005;80:1493–1500.

    Article  PubMed  CAS  Google Scholar 

  3. Chapman LE, Wilson CA. Implications of the advent of homozygous alpha l,3-galactosyltransferase gene-deficient pigs on transmission of infectious agents. Xenotransplantation 2003;10:287–288.

    Article  PubMed  Google Scholar 

  4. Wood JC, Quinn G, Suling KM, Oldmixon BA, Van Tine BA, Cina R, et al. Identification of exogenous forms of human-tropic porcine endogenous retrovirus in miniature swine. J Virol 2004;78:2494–2501.

    Article  PubMed  CAS  Google Scholar 

  5. Quinn G, Wood JC, Ryan DJ, Suling KM, Moran KM, KolberSimonds DL, et al. Porcine endogenous retrovirus transmission characteristics of galactose alpha1–3 galactose-deficient pig cells. J Virol 2004;78:5805–5811.

    Article  PubMed  CAS  Google Scholar 

  6. Levy GA, Ghanekar A, Mendicino M, Phillips MJ, Grant DR. The present status of xenotransplantation. Transplant Proc 2001;33: 3050–3052.

    Article  PubMed  CAS  Google Scholar 

  7. Kues WA, Niemann H. The contribution of farm animals to human health. Trends Biotechnol 2004;22:286–294.

    Article  PubMed  CAS  Google Scholar 

  8. Li M, Zhang D, Hou Y, Jiao L, Zheng X, Wang WH. Isolation and culture of embryonic stem cells from porcine blastocysts. Mol Reprod Dev 2003;65:429–434.

    Article  PubMed  CAS  Google Scholar 

  9. Li M, Ma W, Hou Y, Sun XF, Sun QY, Wang WH. Improved isolation and culture of embryonic stem cells from Chinese miniature pig. J Reprod Dev 2004;50:237–244.

    Article  PubMed  Google Scholar 

  10. Tsung HC, Du ZW, Rui R, Li XL, Bao LP, Wu J, et al. The culture and establishment of embryonic germ (EG) cell lines from Chinese mini swine. Cell Res 2003;13:195–202.

    Article  PubMed  CAS  Google Scholar 

  11. Park KI, Ourednik J, Ourednik V, Taylor RM, Aboody KS, Auguste KI, et al. Global gene and cell replacement strategies via stem cells. Gene Ther 2002;9:613–624.

    Article  PubMed  CAS  Google Scholar 

  12. Molenaar GJ, Hogenesch RI, Sprengers ME, Staal MJ. Ontogenesis of embryonic porcine ventral mesencephalon in the perspective of its potential use as a xenograft in Parkinson’s disease. J Comp Neurol 1997;382:19–28.

    Article  PubMed  CAS  Google Scholar 

  13. Fink JS, Schumacher JM, Ellias SL, Palmer EP, Saint-Hilaire M, Shannon K, et al. Porcine xenografts in Parkinson’s disease and Huntington’s disease patients: Preliminary results. Cell Transplant 2000;9:273–278.

    PubMed  CAS  Google Scholar 

  14. Schumacher JM, Ellias SA, Palmer EP, Kott HS, Dinsmore J, Dempsey PK, et al. Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology 2000;54:1042–1050.

    PubMed  CAS  Google Scholar 

  15. Barker RA, Widner H. Immune problems in central nervous system cell therapy. NeuroRx 2004;1:472–481.

    Article  PubMed  Google Scholar 

  16. Ourednik J, Ourednik V, Lynch WP, Schachner M, Snyder EY. Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons. Nat Biotechnol 2002;20:1103–1110.

    Article  PubMed  CAS  Google Scholar 

  17. Harrower TP, Tyers P, Hooks Y, Barker RA. Long-term survival and integration of porcine expanded neural precursor cell grafts in a rat model of Parkinson’s disease. Exp Neurol 2006;197:56–69.

    Article  PubMed  CAS  Google Scholar 

  18. Mikkelsen M, Moller A, Jensen LH, Pedersen A, Harajehi JB, Pakkenberg H. MPTP-induced Parkinsonism in minipigs: A behavioral, biochemical, and histological study. Neurotoxicol Teratol 1999;21:169–175.

    Article  PubMed  CAS  Google Scholar 

  19. Cumming P, Gillings NM, Jensen SB, Bjarkam C, Gjedde A. Kinetics of the uptake and distribution of the dopamine D(2,3) agonist (R)N-[1-(11)C]n-propylnorapomorphine in brain of healthy and MPTP-treated Gottingen miniature pigs. Nucl Med Biol 2003;30: 547–553.

    Article  PubMed  CAS  Google Scholar 

  20. Matsuyama N, Hadano S, Onoe K, Osuga H, Showguchi-Miyata J, Gondo Y, et al. Identification and characterization of the miniature pig Huntington’s disease gene homolog: Evidence for conservation and polymorphism in the CAG triplet repeat. Genomics 2000;69: 72–85.

    Article  PubMed  CAS  Google Scholar 

  21. Uchida M, Shimatsu Y, Onoe K, Matsuyama N, Niki R, Ikeda JE, et al. Production of transgenic miniature pigs by pronuclear microinjection. Transgenic Res 2001;10:577–582.

    Article  PubMed  CAS  Google Scholar 

  22. Ringe J, Kaps C, Schmitt B, Buscher K, Bartel J, Smolian H, et al. Porcine mesenchymal stem cells. Induction of distinct mesenchymal cell lineages. Cell Tissue Res 2002;307:321–327.

    Article  PubMed  CAS  Google Scholar 

  23. Bosch P, Pratt SL, Stice SL. Isolation, characterization, gene modification, and nuclear reprogramming of porcine mesenchymal stem cells. Biol Reprod 2006;74:46–57.

    Article  PubMed  CAS  Google Scholar 

  24. Moscoso I, Centeno A, Lopez E, Rodriguez-Barbosa JI, Santamarina I, Filgueira P, et al. Differentiation “in vitro” of primary and immortalized porcine mesenchymal stem cells into cardiomyocytes for cell transplantation. Transplant Proc 2005;37:481–482.

    Article  PubMed  CAS  Google Scholar 

  25. Orlic D. BM stem cells and cardiac repair: Where do we stand in 2004? Cytotherapy 2005;7:3–15.

    Article  PubMed  CAS  Google Scholar 

  26. Dib N, Diethrich EB, Campbell A, Gahremanpour A, McGarry M, Opie SR. A percutaneous swine model of myocardial infarction. J Pharmacol Toxicol Methods 2006;53:256–263.

    Article  PubMed  CAS  Google Scholar 

  27. Makkar RR, Price MJ, Lill M, Frantzen M, Takizawa K, Kleisli T, et al. Intramyocardial injection of allogenic bone marrow-derived mesenchymal stem cells without immunosuppression preserves cardiac function in a porcine model of myocardial infarction. J Cardiovasc Pharmacol Ther 2005;10:225–233.

    Article  PubMed  Google Scholar 

  28. Kamihata H, Matsubara H, Nishiue T, Fujiyama S, Tsutsumi Y, Ozono R, et al. Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines. Circulation 2001;104:1046–1052.

    Article  PubMed  CAS  Google Scholar 

  29. Freyman T, Polin G, Osman H, Crary J, Lu M, Cheng L, et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J2006;27:1114–1122.

    Article  Google Scholar 

  30. Dick AJ, Guttman MA, Raman VK, Peters DC, Pessanha BS, Hill JM, et al. Magnetic resonance fluoroscopy allows targeted delivery of mesenchymal stem cells to infarct borders in swine. Circulation 2003;108:2899–2904.

    Article  PubMed  Google Scholar 

  31. Hill JM, Dick AJ, Raman VK, Thompson RB, Yu ZX, Hinds KA, et al. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation 2003;108:1009–1014.

    Article  PubMed  Google Scholar 

  32. Kraitchman DL, Heldman AW, Atalar E, Amado LC, Martin BJ, Pittenger MF, et al. In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 2003; 107: 2290–2293.

    Article  PubMed  Google Scholar 

  33. Carstens MH, Chin M, Li XJ. In situ osteogenesis: Regeneration of 10-cm mandibular defect in porcine model using recombinant human bone morphogenetic protein-2 (rhBMP-2) and Helistat absorbable collagen sponge. J Craniofac Surg 2005;16:1033–1042.

    Article  PubMed  Google Scholar 

  34. Mainil-Varlet P, Rieser F, Grogan S, Mueller W, Saager C, Jakob RP. Articular cartilage repair using a tissue-engineered cartilage-like implant: An animal study. Osteoarthritis Cartilage 2001;9(Suppl A): S6–15.

    Article  PubMed  Google Scholar 

  35. Liu Y, Chen F, Liu W, Cui L, Shang Q, Xia W, et al. Repairing large porcine full-thickness defects of articular cartilage using autologous chondrocyte-engineered cartilage. Tissue Eng 2002;8:709–721.

    Article  PubMed  CAS  Google Scholar 

  36. Sullivan TP, Eaglstein WH, Davis SC, Mertz P. The pig as a model for human wound healing. Wound Repair Regen 2001;9:66–76.

    Article  PubMed  CAS  Google Scholar 

  37. Middelkoop E, van den Bogaerdt AJ, Lamme EN, Hoekstra MJ, Brandsma K, Ulrich MM. Porcine wound models for skin substitution and burn treatment. Biomaterials 2004;25:1559–1567.

    Article  PubMed  CAS  Google Scholar 

  38. Matouskova E, Vogtova D, Konigova R. A recombined skin composed of human keratinocytes cultured on cell-free pig dermis. Burns 1993;19:118–123.

    Article  PubMed  CAS  Google Scholar 

  39. Ito M, Liu Y, Yang Z, Nguyen J, Liang F, Morris RJ, et al. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat Med 2005;11:1351–1354.

    Article  PubMed  CAS  Google Scholar 

  40. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, et al. Defining the epithelial stem cell niche in skin. Science 2004;303:359–363.

    Article  PubMed  CAS  Google Scholar 

  41. Klima J, Smetana K Jr, Motlik J, Plzakova Z, Liu FT, Stork J, et al. Comparative phenotypic characterization of keratinocytes originating from hair follicles. J Mol Histol 2005;36:89–96.

    Article  PubMed  CAS  Google Scholar 

  42. Coyne TM, Akiva JM, Woodbury D, Black IB. Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia. Stem Cells 2006;24(11):2483–2492.

    Article  PubMed  Google Scholar 

  43. Vodicka P, Smetana K Jr, Dvorankova B, Emerick T, Xu YZ, Ourednik J, et al. The miniature pig as an animal model in biomedical research. Ann NY Acad Sci 2005;1049:161–171.

    Article  PubMed  Google Scholar 

  44. Hofmann A, Kessler B, Ewerling S, Weppert M, Vogg B, Ludwig H, et al. Efficient transgenesis in farm animals by lentiviral vectors. EMBO Rep 2003;4:1054–1060.

    Article  PubMed  CAS  Google Scholar 

  45. Nguyen TH, Khakhoulina T, Simmons A, Morel P, Trono D. A simple and highly effective method for the stable transduction of uncultured porcine hepatocytes using lentiviral vector. Cell Transplant 2005;14:489–496.

    PubMed  Google Scholar 

  46. Arbab AS, Yocum GT, Rad AM, Khakoo AY, Fellowes V, Read EJ, et al. Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells. NMR Biomed 2005;18: 553–559.

    Article  PubMed  CAS  Google Scholar 

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© 2008 Humana Press Inc., Totowa, NJ

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Vodicka, P. et al. (2008). The Minipig as an Animal Model in Biomedical Stem Cell Research. In: Conn, P.M. (eds) Sourcebook of Models for Biomedical Research. Humana Press. https://doi.org/10.1007/978-1-59745-285-4_27

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  • DOI: https://doi.org/10.1007/978-1-59745-285-4_27

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-933-8

  • Online ISBN: 978-1-59745-285-4

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