{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:05:27Z","timestamp":1791230727026,"version":"4.1.0"},"reference-count":48,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2008,12,8]],"date-time":"2008-12-08T00:00:00Z","timestamp":1228694400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tissue Engineering Part C: Methods"],"published-print":{"date-parts":[[2009,6,1]]},"abstract":"<jats:p>\n                    Primary cultures of human hepatocytes are a reference cellular model, because they maintain key features of liver cells\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , such as expression of drug-metabolizing enzymes, response to enzyme inducers, and generation of hepatic metabolites. However, there is a restricted availability of primary hepatocytes, and they show phenotypic instability in culture. Thus, different alternatives have been developed to overcome the culture limitations and to mimic\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    tissue material. Herein, culture conditions, such as medium composition, impeller type, and cell inoculum concentration, were optimized in stirred culture vessels and applied to a three-dimensional (3D) bioreactor system. Cultures of rat hepatocytes as 3D structures on bioreactor, better resembling\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    cellular organization, were compared to traditional monolayer cultures. Liver-specific functions, such as albumin and urea secretion, phase I and phase II enzyme activities, and the capacity to metabolize diphenhydramine and troglitazone, were measured over time. Hepatocyte functions were preserved for longer time in the 3D bioreactor than in the monolayer system. Moreover, rat hepatocytes grown in 3D system maintained the ability to metabolize such compounds, as well as\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . Our results indicate that hepatocytes cultured as 3D structures are a qualified model system to study hepatocyte drug metabolism over a long period of time. Moreover, these cultures can be used as feeding systems to obtain cells for other tests in a short time.\n                  <\/jats:p>","DOI":"10.1089\/ten.tec.2008.0352","type":"journal-article","created":{"date-parts":[[2008,12,10]],"date-time":"2008-12-10T10:33:12Z","timestamp":1228905192000},"page":"157-167","source":"Crossref","is-referenced-by-count":72,"title":["Towards an Extended Functional Hepatocyte\n                    <i>In Vitro<\/i>\n                    Culture"],"prefix":"10.1177","volume":"15","author":[{"given":"Joana P.","family":"Miranda","sequence":"first","affiliation":[{"name":"Animal Cell Technology Laboratory, IBET\/ITQB-UNL, Apartado 12, Oeiras, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia B.","family":"Leite","sequence":"additional","affiliation":[{"name":"Animal Cell Technology Laboratory, IBET\/ITQB-UNL, Apartado 12, Oeiras, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Muller-Vieira","sequence":"additional","affiliation":[{"name":"ADME &amp; In Vitro Pharmacology, Pharmacelsus GmbH, Saarbruecken, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armanda","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Animal Cell Technology Laboratory, IBET\/ITQB-UNL, Apartado 12, Oeiras, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel J.T.","family":"Carrondo","sequence":"additional","affiliation":[{"name":"Animal Cell Technology Laboratory, IBET\/ITQB-UNL, Apartado 12, Oeiras, Portugal."},{"name":"FCT\/UNL, Monte Caparica, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M.","family":"Alves","sequence":"additional","affiliation":[{"name":"Animal Cell Technology Laboratory, IBET\/ITQB-UNL, Apartado 12, Oeiras, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2008,12,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2.2.183"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-008X(03)00128-5"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03190200"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(99)00088-5"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.23784"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)37925-X"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026013395001"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/65.2.166"},{"key":"e_1_3_3_10_2","first-page":"288","article-title":"Qualitative study of three cell culture methods","volume":"22","author":"Wang A.","year":"2002","unstructured":"Wang A., , Xia T., , Ran P., , Chen X., , Nuessler A.K. Qualitative study of three cell culture methods. J Huazhong Univ Sci Technolog Med Sci, 22:288\u2013291. 2002.","journal-title":"J Huazhong Univ Sci Technolog Med Sci"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(99)00091-5"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(99)00081-2"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(97)00204-9"},{"key":"e_1_3_3_14_2","first-page":"91","article-title":"The suitability of hepatocyte culture models to study various aspects of drug metabolism","volume":"18","author":"Nussler A.K.","year":"2001","unstructured":"Nussler A.K., , Wang A., , Neuhaus P., , Fischer J., , Yuan J., , Liu L., , Zeilinger K., , Gerlach J., , Arnold P.J., , Albrecht W. The suitability of hepatocyte culture models to study various aspects of drug metabolism. 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Core techniques: measurement of LDH activity. Doyle A., , Griffiths J.B., , Newell D.G. Cell and Tissue Culture: Laboratory Procedures. New York: John Wiley & Sons, 1998; 4B:8.1\u20138.3."},{"key":"e_1_3_3_28_2","first-page":"118","volume-title":"Methods of Enzymatic Analysis","author":"Vassault A.","year":"1983","unstructured":"Vassault A. Lactate dehydrogenase: UV-method with pyruvate and NADH. Bergmeyer H.U., , Grassl M. Methods of Enzymatic Analysis, III. New York: John Wiley & Sons, 1983; 118\u2013126."},{"key":"e_1_3_3_29_2","first-page":"129","volume-title":"Isolation, Culture and Use of Human Hepatocytes in Drug Research","author":"Gomez-Lechon M.J.","year":"1997","unstructured":"Gomez-Lechon M.J., , Donato M.T., , Ponsoda X., , Fabra R., , Trullenque R., , Castell J.V. In vitro methods in pharmaceutical. Castell J., , Gomez-Lechon M. Isolation, Culture and Use of Human Hepatocytes in Drug Research. 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