Abstract
Regenerative medicine requires preclinical trials of new therapies before starting human studies. In this context, animal models play a fundamental role for investigating biological and functional activities of new cells and tissues. The rodent species is extensively used in studies related to stem cell biology, providing important information, but at the same time its use has important limitations for a variety of disease categories because of the different body size and physiology relative to humans. Large animal species, such as dogs, pigs, sheep, cattle, horses, and nonhuman primates, are better predictors of human responses than rodents, but in each case it will be necessary to choose the best model for a specific application.
The knowledge of embryonic and induced pluripotent stem cells, as well as of adult stem cells, requires significant effort for establishing and characterizing cell lines, comparing behavior to human analogues, and testing potential applications.
Herein we describe the current status and advantages of the use of large animal models in stem cell-based regenerative medicine.
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Further Reading
Bao L, He L, Chen J, Wu Z, Liao J, Rao L, et al. Reprogramming of ovine adult fibroblasts to pluripotency via drug-inducible expression of defined factors. Cell Res. 2011;21(4):600–8.
Brevini T, Pennarossa G, Maffei S, Gandolfi F. Pluripotency network in porcine embryos and derived cell lines. Reprod Domest Anim. 2012;47 suppl 4:86–91. doi:10.1111/j.1439-0531.2012.02060.x.
Brevini TA, Antonini S, Cillo F, Crestan M, Gandolfi F. Porcine embryonic stem cells: facts, challenges and hopes. Theriogenology. 2007;68 Suppl 1:S206–13.
Choi SA, Choi HS, Kim KJ, Lee DS, Lee JH, Park JY, et al. Isolation of canine mesenchymal stem cells from amniotic fluid and differentiation into hepatocyte-like cells. In Vitro Cell Dev Biol Anim. 2013;49(1):42–51.
Cibelli J, Emborg ME, Prockop DJ, Roberts M, Schatten G, Rao M, Harding J, Mirochnitchenko O. Strategies for improving animal models for regenerative medicine. Cell Stem Cell. 2013;12(3):271–4.
DABE: http://www.iets.org/comm_dabe.asp?autotry=true&ULnotkn=true
Dattena M, Chessa B, Lacerenza D, Accardo C, Pilichi S, et al. Isolation, culture, and characterization of embryonic cell lines from vitrified sheep blastocysts. Mol Reprod Dev. 2006;73:31–9.
Dixon JA, Spinale FG. Large animal models of heart failure: a critical link in the translation of basic science to clinical practice. Circ Heart Fail. 2009;2(3):262–71.
Doevendans PA, Daemen MJ, de Muinck ED, Smits JF. Cardiovascular phenotyping in mice. Cardiovasc Res. 1998;39(1):34–49.
Fortier LA, Smith RKW. Regenerative medicine for tendinous and ligamentous injuries of sport horses. Vet Clin North Am Equine Pract. 2008;24:191–201.
Gandolfi F, Vanelli A, Pennarossa G, Rahaman M, Acocella F, Brevini TA. Large animal models for cardiac stem cell therapies. Theriogenology. 2011;75(8):1416–25.
Gandolfi F, Pennarossa G, Maffei S, Brevini T. Why is it so difficult to derive pluripotent stem cells in domestic ungulates? Reprod Domest Anim. 2012;47 suppl 5:11–7. doi:10.1111/j.1439-0531.2012.02106.x.
Han X, Han J, Ding F, Cao S, Lim SS, Dai Y, et al. Generation of induced pluripotent stem cells from bovine embryonic fibroblast cells. Cell Res. 2011;21(10):1509–12.
Harding J, Roberts RM, Mirochnitchenko O. Large animal models for stem cell therapy. Stem Cell Res Ther. 2013;4(2):23.
Hayes B, Fagerlie SR, Ramakrishnan A, Baran S, Harkey M, Graf L, et al. Derivation, characterization, and in vitro differentiation of canine embryonic stem cells. Stem Cells. 2008;26:465–73.
Heidari B, Shirazi A, Akhondi MM, Hassanpour H, Behzadi B, Naderi MM, et al. Comparison of proliferative and multilineage differentiation potential of sheep mesenchymal stem cells derived from bone marrow, liver, and adipose tissue. Avicenna J Med Biotechnol. 2013;5(2):104–17.
Kuzmuk KN, Schook LB. Pigs as a model for biomedical sciences. In: Rothschild MF, Ruvinsky A, editors. The genetics of the pig. 2nd ed. Wallingford: CAB International; 2011. p. 426–44.
Lange-Consiglio A, Corradetti B, Bizzaro D, et al. Characterization and potential applications of progenitor-like cells isolated from horse amniotic membrane. J Tissue Eng Regen Med. 2012;6:622–35. doi:10.1002/term.465.
Lange-Consiglio A, Corradetti B, Meucci A, et al. Characteristics of equine mesenchymal stem cells derived from amnion and bone marrow: in vitro proliferative and multilineage potential assessment. Equine Vet J. 2013. doi:10.1111/evj.12052.
Li X, Zhou SG, Imreh MP, Ährlund-Richter L, Allen WR. Horse embryonic stem cell lines from the proliferation of inner cell mass cells. Stem Cells Dev. 2006;15(4):523–31.
Luo J, Suhr ST, Chang EA, Wang K, Ross PJ, Nelson LL, et al. Generation of leukemia inhibitory factor and basic fibroblast growth factor-dependent induced pluripotent stem cells from canine adult somatic cells. Stem Cells Dev. 2011;20(10):1669–78.
McCall FC, Telukuntla KS, Karantalis V, Suncion VY, Heldman AW, Mushtaq M, Williams AR, Hare JM. Myocardial infarction and intramyocardial injection models in swine. Nat Protoc. 2012;7(8):1479–96.
Pashaiasl M, Khodadadi K, Holland MK, Verma PJ. The efficient generation of cell lines from bovine parthenotes. Cell Reprogram. 2010;12(5):571–9.
Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.
Raoufi MF, Tajik P, Dehghan MM, Eini F, Barin A. Isolation and differentiation of mesenchymal stem cells from bovine umbilical cord blood. Reprod Domest Anim. 2011;46(1):95–9. doi:10.1111/j.1439-0531.2010.01594.x.
Saito S, Sawai K, Minamihashi A, Ugai H, Murata T, Yokoyama KK. Derivation, maintenance, and induction of the differentiation in vitro of equine embryonic stem cells. Methods Mol Biol. 2006;329:59–79.
Suzuki S, Iwamoto M, Saito Y, Fuchimoto D, Sembon S, Suzuki M, Mikawa S, Hashimoto M, Aoki Y, Najima Y, Takagi S, Suzuki N, Suzuki E, Kubo M, Mimuro J, Kashiwakura Y, Madoiwa S, Sakata Y, Perry AC, Ishikawa F, Onishi A. Il2rg gene-targeted severe combined immunodeficiency pigs. Cell Stem Cell. 2012;10(6):753–8.
Ulrichs K, Eber S, Schneiker B, Gahn S, Strauß A, Moskalenko V, Chodnevskaja I. Isolation of porcine pancreatic islets for xenotransplantation. Methods Mol Biol. 2012;885:213–32. doi:10.1007/978-1-61779-845-0_13.
Webster RA, Blaber SP, Herbert BR, Wilkins MR, Vesey G. The role of mesenchymal stem cells in veterinary therapeutics: a review. N Z Vet J. 2012;60(5):265–72.
West FD, Terlouw SL, Kwon DJ, Mumaw JL, Dhara SK, Hasneen K, et al. Porcine induced pluripotent stem cells produce chimeric offspring. Stem Cells Dev. 2010;19(8):1211–20.
White FC, Roth DM, Bloor CM. The pig as a model for myocardial ischemia and exercise. Lab Anim Sci. 1986;36(4):351–6.
Wu Z, Chen J, Ren J, Bao L, Liao J, Cui C, et al. Generation of pig induced pluripotent stem cells with a drug-inducible system. J Mol Cell Biol. 2009;1(1):46–54.
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Brevini, T.A.L., Gandolfi, F. (2013). Use of Large Animal Models for Regenerative Medicine. In: Pluripotency in Domestic Animal Cells. SpringerBriefs in Stem Cells. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8053-3_3
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DOI: https://doi.org/10.1007/978-1-4899-8053-3_3
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