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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Genes &amp; Cells</journal-id><journal-title-group><journal-title xml:lang="en">Genes &amp; Cells</journal-title><trans-title-group xml:lang="ru"><trans-title>Гены и Клетки</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>Genes and Cells</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2313-1829</issn><issn publication-format="electronic">2500-2562</issn><publisher><publisher-name xml:lang="en">Human Stem Cells Institute</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">229977</article-id><article-id pub-id-type="doi">10.23868/gc229977</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Original Study Articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Оригинальные исследования</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Are oval cells supposed to be liver stem cells or hepatoblasts?</article-title><trans-title-group xml:lang="ru"><trans-title>Овальные клетки - предполагаемые стволовые клетки печени или гепатобласты?</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kiyasov</surname><given-names>А. P.</given-names></name><name xml:lang="ru"><surname>Киясов</surname><given-names>А. П.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Department of Normal Anatomy</p></bio><bio xml:lang="ru"><p>кафедра нормальной анатомии</p></bio><email>redaktor@celltranspl.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Gumerova</surname><given-names>A. A.</given-names></name><name xml:lang="ru"><surname>Гумерова</surname><given-names>А. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Department of Normal Anatomy</p></bio><bio xml:lang="ru"><p>кафедра нормальной анатомии</p></bio><email>redaktor@celltranspl.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Titova</surname><given-names>M. A.</given-names></name><name xml:lang="ru"><surname>Титова</surname><given-names>М. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Department of Normal Anatomy</p></bio><bio xml:lang="ru"><p>кафедра нормальной анатомии</p></bio><email>redaktor@celltranspl.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Kazan State Medical University</institution></aff><aff><institution xml:lang="ru">Казанский государственный медицинский университет</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2006-02-15" publication-format="electronic"><day>15</day><month>02</month><year>2006</year></pub-date><volume>1</volume><issue>2</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>55</fpage><lpage>58</lpage><history><date date-type="received" iso-8601-date="2023-02-13"><day>13</day><month>02</month><year>2023</year></date><date date-type="accepted" iso-8601-date="2023-02-13"><day>13</day><month>02</month><year>2023</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2006, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2006, Эко-Вектор</copyright-statement><copyright-year>2006</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/></permissions><self-uri xlink:href="https://genescells.ru/2313-1829/article/view/229977">https://genescells.ru/2313-1829/article/view/229977</self-uri><abstract xml:lang="en"><p>The aim of the work is to study the patterns of expression of oval cell markers during prenatal histogenesis of rat and human liver, as well as in human hepatocytes in vitro. The liver of rats was obtained at various gestation periods and during the first month after birth. Human embryos and fetuses are obtained as a result of legal medical abortions. The material was fixed and poured into paraffin according to the standard procedure or cryostatic sections were prepared, then stained with immunohistochemical indirect immunoperoxidase and streptavidin-biotin methods using commercial monoclonal antibodies to cytokeratins-7, -8, -18, -19. Gamma-glutamyl-transpeptidase was detected histochemically. The results of the studies showed that rat and human hepatoblasts express cytokeratin-19 and gamma-glutamyltrans-peptidase, whereas cholangiocytes express cytokeratin-7 (and only since the beginning of the formation of intrahepatic bile ducts). Moreover, human hepatocytes under cultivation begin to express cytokeratin-19 again. The data obtained show that the markers of oval cells (cytokeratin-19 and gamma-glutamyltranspeptidase) are markers of differentiating hepatocytes, which does not allow identifying oval cells with liver stem cells.</p></abstract><trans-abstract xml:lang="ru"><p>Цель работы - изучение закономерностей экспрессии маркеров овальных клеток в ходе пренатального гистогенеза печени крысы и человека, а также в гепатоцитах человека in vitro. Печень крыс получали на различных сроках гестации и в течение первого месяца после рождения. Эмбрионы и плоды человека получены в результате легальных медицинских абортов. Материал фиксировали и заливали в парафин по стандартной методике или готовили криостатные срезы, далее окрашивали иммуногистохимическим непрямым иммунопероксидазным и стрептавидин-биотиновым методами с использованием коммерческих моноклональных антител к цитокератинам-7, -8, -18, -19. Гамма-глутамил- транспептидазу выявляли гистохимически. Результаты исследований показали, что гепатобласты крысы и человека экспрессируют цитокератин-19 и гамма-глутамилтранс- пептидазу, тогда какхолангиоциты экспрессируют цитокератин-7 (и только с момента начала образования внутрипеченочныхжелчных протоков). Более того, гепатоциты человека в условиях культивирования вновь начинают экспрессировать цитокератин-19. Полученные данные показывают, что маркеры овальных клеток (цитокератин-19 и гамма-глутамилтранспептидаза) являются маркерами дифференцирующихся гепатоцитов, что не позволяет отождествлять овальные клетки со стволовыми клетками печени.</p></trans-abstract><kwd-group xml:lang="en"><kwd>oval cells</kwd><kwd>liver</kwd><kwd>liver stem cells</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>овальные клетки</kwd><kwd>печень</kwd><kwd>стволовые клетки печени</kwd></kwd-group><funding-group><funding-statement xml:lang="en">The work was carried out with the financial support of the RFBR (grant 04-04-49164).</funding-statement><funding-statement xml:lang="ru">Работа выполнена при финансовой поддержке РФФИ (грант 04-04-49164).</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Wilson J.W., Leduc E.H. Role of cholangioles in restoration of the liver of the mouse after dietary injury. J. Pathol. Bacteriol. 1958; 76: 441 -9.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Фактор В.М., Радаева С.А. Стволовой резерв печени. Онтогенез 1991; 22(2): 181-9.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Fausto N. Oval cells and liver carcinogenesis: an analysis of cell lineages in hepatic tumors using oncogene transfection techniques. Prog. Clin. Biol. Res. 1990; 331: 325-34.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Sell S. Is there a liver stem cell? Cancer Res. 1990; 50: 3811-5.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Sigal S.H., Brill S., Fiorino A.S., Reid L.M. The liver as a stem cell and lineage system. Am. J. Physiol. 1992; 263: G139-48.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Dabeva M.D., Shafritz D.A. Activation, proliferation, and differentiation of progenitor cells into hepatocytes in the D-galactosamine model of liver regeneration. Am. J. Pathol. 1993; 143(6): 1606-20.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Урываева И.В. Модель репопуляции печени, поврежденной дипином. Бюлл. экспер. биол. мед. 1997; 124(10): 364-8.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Factor V.M., Radaeva S.A., Thorgeirsson S.S. Origin and fate of oval cells in dipin-induced hepatocarcinogenesis in the mouse. Am. J. Pathol. 1994; 145: 409-22.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Braun K.M., Sandgren E.P. Cellular Origin of Regenerating Parenchyma in a Mouse Model of Severe Hepatic Injury Am. J. of Pathol. 2000; 157: 561-9</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Sarraf C., Lalani E.-N., Golding M. et al. Cell behavior in the acetylaminofluorene- treated regenerating rat liver. Am. J. Pathol. 1994; 145: 1114-26.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Evarts R.P., Nakatsukasa H., Marsden E.R. et al. Cellular and molecular changes in the early stages of chemical hepatocarcinogenesis in the rat. Cancer Res. 1990; 50: 3439-44.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Hsia C.C., Evarts R.P., Nakatsukasa H. et al. Occurrence of oval cell in hepatitis B virus associated human hepatocarcinogenesis. Hepatology 1992; 67: 427-33.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Chen Y.-K., Zhao X.-X., Li J.-G. et al. Ductular proliferation in liver tissues with severe chronic hepatitis B: An immunohistochemical study. World J. Gastroenterol. 2006; 12(9): 1443-6</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Parent R., Marion M.J., Furio L. et al. Origin and characterization of a human bipotent liver progenitor cell line. Gastroenterology 2004; 126(4): 1147-56.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>He Z.P., Tan. W.G., Tang Y.F. et al. Activation, isolation, identification and in vitro proliferation of oval cells from adult rat liver. Cell Prolif. 2004; 37(2): 177-87.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Crosby H.A., Kelly D.A., Strain A.J. Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium. Gastroenterology 2001;120(2):534-44.</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Paku S., Dezso K., Kopper L., Nagy P. Immunohistochemical analysis of cytokeratin 7 expression in resting and proliferating biliary structures of rat liver. Hepatology 2005; 42(4): 863-70.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Yavorkovsky L., Lai E., Ilic Z., Sell S. Participation of small intraportal stem cells in the restitutive response of the liver to portal necrosis induced by allyl alcohol. Hepatology 1995; 21: 1702-12.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Hixson D.C., Faris R.A., Thompson N.L. An antigenic portrrait of the liver during carcinogenesis. Pathobiology 1990; 58: 65-77.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Dunsford H.A., Sell S. Production of monoclonal antibodies to preneoplastic liver cell populations induced by chemical carcinogens in rats and to transplantable Morris Hepatomas. Cancer Res. 1989; 49: 4887-93.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Engelhardt N.V., Factor V.M., Medvinsky A.L. et al. Common antigen of oval and biliary epithelial cells (A6) is a differentiation marker of epithelial and erythroid cell lineages in early development of the mouse. Differentiation 1993; 55: 19-26.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Rijnties P., Moshage H., Van Gemert P. et al. Cryopreservation of adult human hepatocytes. The influence of deep freezing storage on the viability, cell seeding, survival, fine structures and albumin synthesis in prymary cultures. J. Hepatol. 1986; 3: 7-18.</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Moshage H., Rijnies P., Hatkenscheiol M. et al. Primary culture of cryopreserved adult human hepatocytes on homologous extracellular matrix and the influence of monocytic products on albumin synthesis. J. Hepatol. 1988; 7: 34-44.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Rutenburg A.M., Kim H., Fischbein J.W. et al. Histochemical and ultrastructural demonstration of g-Glutamil transpeptidase activity. J. Histochem. Cytochem. 1969; 17: 517-26.</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Shiojiri N. Transient expression of bile-duct-specific cytokeratin in fetal mouse hepatocytes. Cell Tissue. Res. 1994; 278: 117-23.</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Bisgaard H.C., Parmelee D.C., Dunsford H.A. et al. Keratin 14 protein in cultured nonparenchymal rat hepatic epithelial cells: characterization of keratin 14 and keratin 19 as antigens for the commonly used mouse monoclonal antibody OV-6. Molec. Carcinogenesis. 1993; 7: 60-6.</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Van Eyken P., Desmet V. Cytokeratins and the liver. Liver 1993; 13: 113-22.</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Thorgeirsson S.S. Target cell populations in virus-associated hepatocarcinogenesis. Princess Takamatsu Symp. 1995; 25: 163-70.</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Demetris A.J., Seaberg E.C., Wennerberg A. et al. Ductular reaction after submassive necrosis in humans. Special emphasis on analysis of ductular hepatocytes. Am. J. Pathol. 1996; 149(2): 439-48.</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Haque S., Haruna Y., Saito K. et al. Identification of bipotential progenitor cells in human liver regeneration. Lab. Invest. 1996; 75(5): 699-705.</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Глейберман А.С., Трояновский С.М., Банников Г.А. Перестройка цитоскелета в гепатоцитах регенерирующей печени мышей. Бюлл. экспер. биол. мед. 1984; 12: 741-3.</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Notenboom R.G., De-Boer P.A., Moorman A.F., Lamers W. The establishment of the hepatic architecture is a prerequisite for the development of lobular pattern of gene expression. Development 1996; 122(1): 321-32.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Pagan R., Martin I., Alonso A. et al. Vimentin filaments follow preexisting cytokeratin network during epithelial-mesenchymal transition of cultured neonatal rat hepatocytes. Exp. Cell Res. 1996; 222(2): 333-44.</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Киясов А.П., Гумерова А.А., Петров С.В., Яп С.Х. Реэкспрессия цитокератина-19 в первичной культуре гепатоцитов человека. Бюлл. экспер. биол. мед. 1998; 126(7): 118-20.</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Blaheta R.A., Kronenberger B., Woitaschek D. et al. Dedifferentiation of human hepatocytes by extracellular matrix proteins in vitro: quantitative and qualitative investigation of cytokeratin 7, 8, 18, 19 and vimentin filaments. J. Hepatol. 1998; 28(4): 677-90.</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Menthena 1. A., Deb N., Oertel M. et al. Bone Marrow Progenitors Are Not the Source of Expanding Oval Cells in Injured Liver Stem Cells 2004; 22: 1049-61.</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Paku S., Schnur J., Nagy P., Snorri S. Thorgeirsson. Origin and Structural Evolution of the Early Proliferating Oval Cells in Rat Liver Am. J. Pathol. 2001 ; 158: 1313-23.</mixed-citation></ref></ref-list></back></article>
