<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.4 20241031//EN"
        "https://jats.nlm.nih.gov/publishing/1.4/JATS-journalpublishing1-4.dtd">
<article  article-type="research-article"        dtd-version="1.4">
            <front>

                <journal-meta>
                                                                <journal-id>ankara univ vet fak derg</journal-id>
            <journal-title-group>
                                                                                    <journal-title>Ankara Üniversitesi Veteriner Fakültesi Dergisi</journal-title>
            </journal-title-group>
                            <issn pub-type="ppub">1300-0861</issn>
                                        <issn pub-type="epub">1308-2817</issn>
                                                                                            <publisher>
                    <publisher-name>Ankara University</publisher-name>
                </publisher>
                    </journal-meta>
                <article-meta>
                                        <article-id pub-id-type="doi">10.33988/auvfd.682682</article-id>
                                                                <article-categories>
                                            <subj-group  xml:lang="en">
                                                            <subject>Veterinary Surgery</subject>
                                                    </subj-group>
                                            <subj-group  xml:lang="tr">
                                                            <subject>Veteriner Cerrahi</subject>
                                                    </subj-group>
                                    </article-categories>
                                                                                                                                                        <title-group>
                                                                                                                        <article-title>Pilot study on cardiogenic differentiation capability of rabbit mesenchymal stem cells</article-title>
                                                                                                                                        </title-group>
            
                                                    <contrib-group content-type="authors">
                                                                        <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0001-5749-7773</contrib-id>
                                                                <name>
                                    <surname>Grıgorova</surname>
                                    <given-names>Natalia</given-names>
                                </name>
                                                                    <aff>Trakia University, Faculty of Veterinary Medicine, Department of Pharmacology, Animal Physiology and Physiological Chemistry, Stara Zagora</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0001-7720-4720</contrib-id>
                                                                <name>
                                    <surname>Gócza</surname>
                                    <given-names>Elen</given-names>
                                </name>
                                                                    <aff>Applied Embryology and Stem Cell Research Group, Department of Animal Biotechnology, Gödöllö</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-9291-332X</contrib-id>
                                                                <name>
                                    <surname>Vachkova</surname>
                                    <given-names>Ekaterina</given-names>
                                </name>
                                                                    <aff>Trakia University, Faculty of Veterinary Medicine, Department of Pharmacology, Animal Physiology and Physiological Chemistry, Stara Zagora</aff>
                                                            </contrib>
                                                                                </contrib-group>
                        
                                        <pub-date pub-type="pub" iso-8601-date="20200901">
                    <day>09</day>
                    <month>01</month>
                    <year>2020</year>
                </pub-date>
                                        <volume>67</volume>
                                        <issue>4</issue>
                                        <fpage>407</fpage>
                                        <lpage>412</lpage>
                        
                        <history>
                                    <date date-type="received" iso-8601-date="20200131">
                        <day>01</day>
                        <month>31</month>
                        <year>2020</year>
                    </date>
                                                    <date date-type="accepted" iso-8601-date="20200506">
                        <day>05</day>
                        <month>06</month>
                        <year>2020</year>
                    </date>
                            </history>
                                        <permissions>
                    <copyright-statement>Copyright © 1954, Ankara Üniversitesi Veteriner Fakültesi Dergisi</copyright-statement>
                    <copyright-year>1954</copyright-year>
                    <copyright-holder>Ankara Üniversitesi Veteriner Fakültesi Dergisi</copyright-holder>
                </permissions>
            
                                                                                                <abstract><p>Cardiovascular diseases are still one of the most common reasons for mortality in humans. Mesenchymal stem cells (MSCs) are preferable in cardiac regeneration cell-based therapies because of their allogeneic and high proliferative potential. The electrophysiological properties of the rabbit heard is closer to human than the mouse. The current study aimed to trace mRNA expression changes of two stemness/cardiogenic differentiation ability-related transcriptionala factors OCT4 and GATA4 in rabbit MSCs during early stages of induced cardiomyocyte differentiation in vitro. The mesenchymal stem cell originated from different anatomical areas-subcutaneous, visceral, bone marrow and pericardial tissue. The cardiac differentiation protocol for mouse embryonic stem cells in hanging drop was adopted in rabbit MSCs. The best formed embryonal bodies (EBs) like structures were collected and cultivated on gelatin-coated plates. The total mRNA was obtained before cardiac differentiation and on the 6th day after it. SYBER based real-time PCR was performed to evaluate the mRNA expression fold-changes of OCT4 and GATA4. The cultivation of MSCs in hanging drops during cardiac differentiation induced EBs formation, without any contractile activity up to the 6th day of the differentiation in all cell types. The applied differentiation protocol significantly downregulated GATA4 expression in ADSCs - EBs, while in BMSCs, both target genes were significantly upregulated. In conclusion, the adopted cardiac differentiation protocol from mouse embryonic stem cells could be a useful approach for rabbit bone marrow mesenchymal stem cells. Since the rest of the cells revealed weak cardiogenic capability at this early stage, some modifications of induction protocols should be considered.</p></abstract>
                                                                                    
            
                                                            <kwd-group>
                                                    <kwd>Cardiogenic differentiation</kwd>
                                                    <kwd>  mesenchymal stem cells</kwd>
                                                    <kwd>  rabbit</kwd>
                                            </kwd-group>
                                                        
                                                                                                                                                    </article-meta>
    </front>
    <back>
                            <ref-list>
                                    <ref id="ref1">
                        <label>1</label>
                        <mixed-citation publication-type="journal">1.	Anonymous (2017):World Health Organization (WHO). Available at: https://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds). (Accessed 17 May 2017).</mixed-citation>
                    </ref>
                                    <ref id="ref2">
                        <label>2</label>
                        <mixed-citation publication-type="journal">2.	Baer PC (2014): Adipose-derived mesenchymal stromal/stem cells: An update on their phenotype in vivo and in vitro. World J Stem Cells, 6, 256-65.</mixed-citation>
                    </ref>
                                    <ref id="ref3">
                        <label>3</label>
                        <mixed-citation publication-type="journal">3.	Baer PC, Geiger H (2012): Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells Int, 2012, 812693.</mixed-citation>
                    </ref>
                                    <ref id="ref4">
                        <label>4</label>
                        <mixed-citation publication-type="journal">4.	Baer PC, Griesche N, Luttmann W, et al (2010): Human adipose-derived mesenchymal stem cells in vitro: evaluation of an optimal expansion medium preserving stemness. Cytotherapy, 12, 96-106.</mixed-citation>
                    </ref>
                                    <ref id="ref5">
                        <label>5</label>
                        <mixed-citation publication-type="journal">5.	Burridge P, Keller G, Gold JD, et al (2012): Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell, 10, 16-28.</mixed-citation>
                    </ref>
                                    <ref id="ref6">
                        <label>6</label>
                        <mixed-citation publication-type="journal">6.	Choi YS, Dusting GJ, Stubbs S, et al (2010): Differentiation of human adipose-derived stem cells into beating cardiomyocytes. J Cell Mol Med, 14, 878-889.</mixed-citation>
                    </ref>
                                    <ref id="ref7">
                        <label>7</label>
                        <mixed-citation publication-type="journal">7.	Conrad C, Huss R (2005): Adult stem cell lines in regenerative medicine and reconstructive surgery. J Surg Res, 124, 201-208.</mixed-citation>
                    </ref>
                                    <ref id="ref8">
                        <label>8</label>
                        <mixed-citation publication-type="journal">8.	Dulak J, Szade K, Szade A, et al (2015): Adult stem cells: hopes and hypes of regenerative medicine. Acta Biochim Pol, 62, 329-37</mixed-citation>
                    </ref>
                                    <ref id="ref9">
                        <label>9</label>
                        <mixed-citation publication-type="journal">9.	Ejaz A, Hatzmann  FM, Hammerle S, et al (2019): Fibroblast feeder layer supports adipogenic differentiation of human adipose stromal/progenitor cells. Adipocyte, 8, 178-189.</mixed-citation>
                    </ref>
                                    <ref id="ref10">
                        <label>10</label>
                        <mixed-citation publication-type="journal">10.	Ferroni L, Gardin C, Bellin G, et al (2019): Bovine pericardium membrane as new tool for mesenchymal stem cells commitment. J Tissue Eng Regen Med, 13, 1805-1814.</mixed-citation>
                    </ref>
                                    <ref id="ref11">
                        <label>11</label>
                        <mixed-citation publication-type="journal">11.	Gaetani R, Yin C, Srikumar N, et al (2016): Cardiac-derived extracellular matrix enhances cardiogenic properties of human cardiac progenitor cells. Cell Transplantation, 25, 1653-1663.</mixed-citation>
                    </ref>
                                    <ref id="ref12">
                        <label>12</label>
                        <mixed-citation publication-type="journal">12.	Greco SJ, Liu K, Rameshwar P (2007): Functional similarities among genes regulated by OCT4 in human mesenchymal and embryonic stem cells. Stem Cells,  25, 3143-3154.</mixed-citation>
                    </ref>
                                    <ref id="ref13">
                        <label>13</label>
                        <mixed-citation publication-type="journal">13.	Iacobellis G, Corradi D, Sharma AM (2005): Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart. Nature Clinical Practice Cardiovascular Medicine, 2, 5365-43.</mixed-citation>
                    </ref>
                                    <ref id="ref14">
                        <label>14</label>
                        <mixed-citation publication-type="journal">14.	Khorramirouz R, Go JL, Noble C, et al (2019): In vivo response of acellular porcine pericardial for tissue engineered transcatheter aortic valves. Sci Rep, 9, 1094.</mixed-citation>
                    </ref>
                                    <ref id="ref15">
                        <label>15</label>
                        <mixed-citation publication-type="journal">15.	Kocan B, Maziarz A, Tabarkiewicz J, et al (2017): Trophic activity and phenotype of adipose tissue-derived mesenchymal stem cells as a background of their regenerative potential. Stem Cells Int, 2017, 1653254.</mixed-citation>
                    </ref>
                                    <ref id="ref16">
                        <label>16</label>
                        <mixed-citation publication-type="journal">16.	Ladage D, Turnbull IC, Ishikawa K, et al (2011): Delivery of gelfoam-enabled cells and vectors into the pericardial space using a percutaneous approach in a porcine model. Gene Therapy, 18, 979-985.</mixed-citation>
                    </ref>
                                    <ref id="ref17">
                        <label>17</label>
                        <mixed-citation publication-type="journal">17.	Limana F, Bertolami C, Mangoni A, et al  (2010): Myocardial infarction induces embryonic reprogramming of epicardial c-kit(+) cells: role of the pericardial fluid. J Mol Cell Cardiol, 48, 609-618.</mixed-citation>
                    </ref>
                                    <ref id="ref18">
                        <label>18</label>
                        <mixed-citation publication-type="journal">18.	Major P, Baczkó I, Hiripi L, et al (2016): A novel transgenic rabbit model with reduced repolarization reserve: long QT syndrome caused by a dominant-negative mutation of the KCNE1 gene. B J Pharmacol, 173, 2046-61.</mixed-citation>
                    </ref>
                                    <ref id="ref19">
                        <label>19</label>
                        <mixed-citation publication-type="journal">19.	Maraghechi P, Hiripi L, Tóth G, et al (2013): Discovery of pluripotency-associated microRNAs in rabbit preimplantation embryos and embryonic stem-like cells. Reproduction, 145, 421-37.</mixed-citation>
                    </ref>
                                    <ref id="ref20">
                        <label>20</label>
                        <mixed-citation publication-type="journal">20.	Minteer D, Marra KG, Rubin JP (2013): Adipose-derived mesenchymal stem cells: biology and potential applications. Adv Biochem Eng Biotechnol, 129, 59-71.</mixed-citation>
                    </ref>
                                    <ref id="ref21">
                        <label>21</label>
                        <mixed-citation publication-type="journal">21.	Naderi N, Combellack EJ, Griffin M, et al (2017): The regenerative role of adipose‐derived stem cells (ADSC) in plastic and reconstructive surgery. Int Wound J, 14, 112-124.</mixed-citation>
                    </ref>
                                    <ref id="ref22">
                        <label>22</label>
                        <mixed-citation publication-type="journal">22.	Navarrete SA, Ramin N, Tonack S, et al (2008): Cell lineagespecific signaling of insulin and insulin-like growth factor I in rabbit blastocysts. Endocrinology, 149, 515–524.</mixed-citation>
                    </ref>
                                    <ref id="ref23">
                        <label>23</label>
                        <mixed-citation publication-type="journal">23.	Nerbonne JM (2004): Studying cardiac arrhythmias in the mouse—a reasonable model for probing mechanisms? Trends Cardiovasc Med, 14, 83-93.</mixed-citation>
                    </ref>
                                    <ref id="ref24">
                        <label>24</label>
                        <mixed-citation publication-type="journal">24.	Nerbonne JM, Kass RS (2005): Molecular physiology of cardiac repolarization. Physiol Rev, 85, 1205-1253.</mixed-citation>
                    </ref>
                                    <ref id="ref25">
                        <label>25</label>
                        <mixed-citation publication-type="journal">25.	Pekkanen-Mattila  M, Ojala M, Kerkelä E, et al (2012): The effect of human and mouse fibroblast feeder cells on cardiac differentiation of human pluripotent stem cells. Stem Cells Int, 2012, 875059.</mixed-citation>
                    </ref>
                                    <ref id="ref26">
                        <label>26</label>
                        <mixed-citation publication-type="journal">26.	Perrino C, Rockman HA (2006): GATA4 and the two sides of gene expression reprogramming. Circ Res, 98, 715-6.</mixed-citation>
                    </ref>
                                    <ref id="ref27">
                        <label>27</label>
                        <mixed-citation publication-type="journal">27.	Pierantozzi E, Gava B, Manini I, et al (2011): Pluripotency regulators in human mesenchymal stem cells: expression of NANOG but not of OCT-4 and SOX-2. Stem Cells, 20, 915-23.</mixed-citation>
                    </ref>
                                    <ref id="ref28">
                        <label>28</label>
                        <mixed-citation publication-type="journal">28.	Sacks HS, Fain JN (2007): Human epicardial adipose tissue: a review. Am Heart J, 153, 907-917.</mixed-citation>
                    </ref>
                                    <ref id="ref29">
                        <label>29</label>
                        <mixed-citation publication-type="journal">29.	Sanina C, Hare JM (2015): Mesenchymal stem cells as a biological drug for heart disease: where are we with cardiac cell-based therapy? Circ Res, 117, 229-233.</mixed-citation>
                    </ref>
                                    <ref id="ref30">
                        <label>30</label>
                        <mixed-citation publication-type="journal">30.	Vachkova E, Bosnakovski D, Yonkova P, et al (2016): Adipogenic potential of stem cells derived from rabbit subcutaneous and visceral adipose tissue in vitro. In Vitro Cell Dev Biol Anim, 52, 829-837.</mixed-citation>
                    </ref>
                                    <ref id="ref31">
                        <label>31</label>
                        <mixed-citation publication-type="journal">31.	Wobus AM, Holzhausen H, Jäkel P, et al (1984): Characterization of a pluripotent stem cell line derived from a mouse embryo. Exp Cell Res, 152, 212-219.</mixed-citation>
                    </ref>
                                    <ref id="ref32">
                        <label>32</label>
                        <mixed-citation publication-type="journal">32.	Wystrychowski W, Patlolla B, Zhuge Y, et al (2016): Multipotency and cardiomyogenic potential of human adipose-derived stem cells from epicardium, pericardium, and omentum. Stem Cell Res Ther, 7, 84.</mixed-citation>
                    </ref>
                                    <ref id="ref33">
                        <label>33</label>
                        <mixed-citation publication-type="journal">33.	Yannarelli G, Pacienza N, Montanari S, et al (2017): OCT4 expression mediates partial cardiomyocyte reprogramming of mesenchymal stromal cells. PLoS One, 12, 1-20.</mixed-citation>
                    </ref>
                                    <ref id="ref34">
                        <label>34</label>
                        <mixed-citation publication-type="journal">34.	Zhang J, Wu Z, Fan Z, et al (2018): Pericardial application as a new route for implanting stem-cell cardiospheres to treat myocardial infarction. J Physiol, 596, 2037-2054.</mixed-citation>
                    </ref>
                                    <ref id="ref35">
                        <label>35</label>
                        <mixed-citation publication-type="journal">35.	Zhang Y, Wu J, King JH, et al (2014): Measurement and interpretation of electrocardiographic QT intervals in murine hearts. Am J Physiol Heart Circ Physiol, 306, 1553-1557.</mixed-citation>
                    </ref>
                                    <ref id="ref36">
                        <label>36</label>
                        <mixed-citation publication-type="journal">36.	Zhu Y, Liu T, Song K, et al  (2008): Adipose-derived stem cell: a better stem cell than BMSC. Cell Res, 18, 165.</mixed-citation>
                    </ref>
                            </ref-list>
                    </back>
    </article>
