Induced pluripotent stem cell lines derived from equine fibroblasts.
Abstract: The domesticated horse represents substantial value for the related sports and recreational fields, and holds enormous potential as a model for a range of medical conditions commonly found in humans. Most notable of these are injuries to muscles, tendons, ligaments and joints. Induced pluripotent stem (iPS) cells have sparked tremendous hopes for future regenerative therapies of conditions that today are not possible to cure. Equine iPS (EiPS) cells, in addition to bringing promises to the veterinary field, open up the opportunity to utilize horses for the validation of stem cell based therapies before moving into the human clinical setting. In this study, we report the generation of iPS cells from equine fibroblasts using a piggyBac (PB) transposon-based method to deliver transgenes containing the reprogramming factors Oct4, Sox2, Klf4 and c-Myc, expressed in a temporally regulated fashion. The established iPS cell lines express hallmark pluripotency markers, display a stable karyotype even during long-term culture, and readily form complex teratomas containing all three embryonic germ layer derived tissues upon in vivo grafting into immunocompromised mice. Our EiPS cell lines hold the promise to enable the development of a whole new range of stem cell-based regenerative therapies in veterinary medicine, as well as aid the development of preclinical models for human applications. EiPS cell could also potentially be used to revive recently extinct or currently threatened equine species.
Publication Date: 2011-02-25 PubMed ID: 21347602PubMed Central: PMC3137777DOI: 10.1007/s12015-011-9239-5Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper describes the creation of pluripotent stem cells from horse fibroblasts. These cells have the potential to aid in the development of new regenerative therapies in veterinary medicine and could also be used in preclinical models for human applications.
Background
- The research focuses on the significant value of the domesticated horse in sports, recreational fields, and as a model for studying a range of medical conditions commonly found in humans, particularly injuries to muscles, tendons, ligaments, and joints.
- Induced pluripotent stem (iPS) cells have sparked significant interest in regenerative therapies that could potentially cure conditions that are currently incurable.
- By creating equine iPS (EiPS) cells, the researchers aim to not only benefit the veterinary field but also validate stem cell-based therapies before moving into human clinical trials.
Methodology
- The study involved the generation of iPS cells from horse fibroblasts. This was done using a piggyBac (PB) transposon-based method to deliver transgenes containing the reprogramming factors Oct4, Sox2, Klf4, and c-Myc, which were expressed in a temporally regulated way.
Findings
- They successfully established iPS cell lines which expressed hallmark pluripotency markers. These cells display a stable karyotype even during long-term culture and they readily form complex teratomas comprising all three embryonic germ layer-derived tissues upon in vivo grafting into immunocompromised mice.
- The study concludes that these EiPS cell lines hold great promise in advancing the development of stem cell-based regenerative therapies in veterinary medicine.
- Moreover, they could aid in the development of preclinical models for human applications. Additionally, it is suggested that EiPS cells could potentially be used to revive recently extinct or currently threatened horse species.
Cite This Article
APA
Nagy K, Sung HK, Zhang P, Laflamme S, Vincent P, Agha-Mohammadi S, Woltjen K, Monetti C, Michael IP, Smith LC, Nagy A.
(2011).
Induced pluripotent stem cell lines derived from equine fibroblasts.
Stem Cell Rev Rep, 7(3), 693-702.
https://doi.org/10.1007/s12015-011-9239-5 Publication
Researcher Affiliations
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
MeSH Terms
- Animals
- Cell Culture Techniques
- Cell Line
- Cell- and Tissue-Based Therapy / methods
- Cells, Cultured
- Cellular Reprogramming
- Fibroblasts / cytology
- Fibroblasts / physiology
- Horses
- Humans
- Induced Pluripotent Stem Cells / cytology
- Induced Pluripotent Stem Cells / physiology
- Kruppel-Like Factor 4
- Mice
- Regeneration
- Transgenes
Conflict of Interest Statement
The authors declare no potential conflicts of interest.
References
This article includes 31 references
- Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos.. Nature 1981 Jul 9;292(5819):154-6.
- Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells.. Proc Natl Acad Sci U S A 1981 Dec;78(12):7634-8.
- Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P, Smith A. The ground state of embryonic stem cell self-renewal.. Nature 2008 May 22;453(7194):519-23.
- Buehr M, Meek S, Blair K, Yang J, Ure J, Silva J, McLay R, Hall J, Ying QL, Smith A. Capture of authentic embryonic stem cells from rat blastocysts.. Cell 2008 Dec 26;135(7):1287-98.
- Demers SP, Smith LC. Derivation, culture, and in vivo developmental capacity of embryonic cell lines from rat blastocysts.. Methods Mol Biol 2010;597:179-88.
- Li X, Zhou SG, Imreh MP, Ahrlund-Richter L, Allen WR. Horse embryonic stem cell lines from the proliferation of inner cell mass cells.. Stem Cells Dev 2006 Aug;15(4):523-31.
- Saito S, Ugai H, Sawai K, Yamamoto Y, Minamihashi A, Kurosaka K, Kobayashi Y, Murata T, Obata Y, Yokoyama K. Isolation of embryonic stem-like cells from equine blastocysts and their differentiation in vitro.. FEBS Lett 2002 Nov 20;531(3):389-96.
- Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells.. Nature 2007 Jul 19;448(7151):313-7.
- Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.. Cell 2006 Aug 25;126(4):663-76.
- Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors.. Cell 2007 Nov 30;131(5):861-72.
- Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells.. Science 2007 Dec 21;318(5858):1917-20.
- Liu H, Zhu F, Yong J, Zhang P, Hou P, Li H, Jiang W, Cai J, Liu M, Cui K, Qu X, Xiang T, Lu D, Chi X, Gao G, Ji W, Ding M, Deng H. Generation of induced pluripotent stem cells from adult rhesus monkey fibroblasts.. Cell Stem Cell 2008 Dec 4;3(6):587-90.
- Liao J, Cui C, Chen S, Ren J, Chen J, Gao Y, Li H, Jia N, Cheng L, Xiao H, Xiao L. Generation of induced pluripotent stem cell lines from adult rat cells.. Cell Stem Cell 2009 Jan 9;4(1):11-5.
- Shimada H, Nakada A, Hashimoto Y, Shigeno K, Shionoya Y, Nakamura T. Generation of canine induced pluripotent stem cells by retroviral transduction and chemical inhibitors.. Mol Reprod Dev 2010 Jan;77(1):2.
- Esteban MA, Xu J, Yang J, Peng M, Qin D, Li W, Jiang Z, Chen J, Deng K, Zhong M, Cai J, Lai L, Pei D. Generation of induced pluripotent stem cell lines from Tibetan miniature pig.. J Biol Chem 2009 Jun 26;284(26):17634-40.
- Ezashi T, Telugu BP, Alexenko AP, Sachdev S, Sinha S, Roberts RM. Derivation of induced pluripotent stem cells from pig somatic cells.. Proc Natl Acad Sci U S A 2009 Jul 7;106(27):10993-8.
- Wu Y, Zhang Y, Mishra A, Tardif SD, Hornsby PJ. Generation of induced pluripotent stem cells from newborn marmoset skin fibroblasts.. Stem Cell Res 2010 May;4(3):180-8.
- Honda A, Hirose M, Hatori M, Matoba S, Miyoshi H, Inoue K, Ogura A. Generation of induced pluripotent stem cells in rabbits: potential experimental models for human regenerative medicine.. J Biol Chem 2010 Oct 8;285(41):31362-9.
- Nathan S, Das De S, Thambyah A, Fen C, Goh J, Lee EH. Cell-based therapy in the repair of osteochondral defects: a novel use for adipose tissue.. Tissue Eng 2003 Aug;9(4):733-44.
- Taylor SE, Smith RK, Clegg PD. Mesenchymal stem cell therapy in equine musculoskeletal disease: scientific fact or clinical fiction?. Equine Vet J 2007 Mar;39(2):172-80.
- Frisbie DD, Smith RK. Clinical update on the use of mesenchymal stem cells in equine orthopaedics.. Equine Vet J 2010 Jan;42(1):86-9.
- Wilke MM, Nydam DV, Nixon AJ. Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model.. J Orthop Res 2007 Jul;25(7):913-25.
- Cohen S, Leshansky L, Zussman E, Burman M, Srouji S, Livne E, Abramov N, Itskovitz-Eldor J. Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues.. Tissue Eng Part A 2010 Oct;16(10):3119-37.
- Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins.. Cell Stem Cell 2009 Jun 5;4(6):472-6.
- Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors.. Science 2008 Nov 7;322(5903):949-53.
- Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced pluripotent stem cells generated without viral integration.. Science 2008 Nov 7;322(5903):945-9.
- Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y, Siuzdak G, Schöler HR, Duan L, Ding S. Generation of induced pluripotent stem cells using recombinant proteins.. Cell Stem Cell 2009 May 8;4(5):381-4.
- Wang W, Lin C, Lu D, Ning Z, Cox T, Melvin D, Wang X, Bradley A, Liu P. Chromosomal transposition of PiggyBac in mouse embryonic stem cells.. Proc Natl Acad Sci U S A 2008 Jul 8;105(27):9290-5.
- Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K. Virus-free induction of pluripotency and subsequent excision of reprogramming factors.. Nature 2009 Apr 9;458(7239):771-5.
- Lin T, Ambasudhan R, Yuan X, Li W, Hilcove S, Abujarour R, Lin X, Hahm HS, Hao E, Hayek A, Ding S. A chemical platform for improved induction of human iPSCs.. Nat Methods 2009 Nov;6(11):805-8.
- Paris DB, Stout TA. Equine embryos and embryonic stem cells: defining reliable markers of pluripotency.. Theriogenology 2010 Sep 1;74(4):516-24.
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