{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:22:59Z","timestamp":1787235779430,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2008,5,16]],"date-time":"2008-05-16T00:00:00Z","timestamp":1210896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Bone marrow\u2010derived liver stem cells (BDLSCs) are very robust cells that can differentiate into liver epithelial cells. These stem cells are promising targets for gene therapy treatment of liver diseases. Liver fibrosis results from chronic liver damage characterized by an accumulation of extracellular matrix (ECM) and levels of urokinase\u2010type plasminogen activator (uPA) play an important role in ECM degradation. In the present study, we investigated the therapeutic effects of uPA gene\u2010modified BDLSC transplantation on carbon tetrachloride (CCl\n                      <jats:sub>4<\/jats:sub>\n                      )\u2010induced liver fibrosis in rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      BDLSCs were obtained from the bone marrow of cholestatic rats. These stem cells were selected and proliferated in medium containing 5% cholestatic serum. BDLSCs transfected with adenovirus\u2010mediated human urokinase\u2010plasminogen activator were transplanted into rats with CCl\n                      <jats:sub>4<\/jats:sub>\n                      \u2010induced hepatic fibrosis. Liver function and the area of hepatic fibrosis were correlated with the development and prognosis of hepatic fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hepatocyte\u2010like colony\u2010forming units were formed by bone marrow cells after 2 weeks in culture. In the uPA gene\u2010modified BDLSC group, the areas of hepatic fibrosis were smaller and liver function was markedly ameliorated compared to controls. The expression of \u03b1\u2010smooth muscle actin protein, transforming growth factor\u2010\u03b21 protein and collagen types I and III mRNA were downregulated. By contrast, the levels of matrix metalloproteinases\u20102, \u20103 and \u20109 mRNA, hepatic growth factor mRNA and proliferating cell nuclear antigen protein increased.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Transplantation of uPA gene\u2010modified BDLSCs may suppress hepatic fibrosis and ameliorate liver function. Copyright \u00a9 2008 John Wiley &amp; Sons, Ltd.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jgm.1206","type":"journal-article","created":{"date-parts":[[2008,5,16]],"date-time":"2008-05-16T05:46:26Z","timestamp":1210916786000},"page":"855-866","source":"Crossref","is-referenced-by-count":13,"title":["Transplantation of urokinase\u2010type plasminogen activator gene\u2010modified bone marrow\u2010derived liver stem cells reduces liver fibrosis in rats"],"prefix":"10.1002","volume":"10","author":[{"given":"Chao","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding\u2010Guo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan\u2010Wen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao\u2010Can","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao\u2010Ling","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Ming","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,5,16]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5712"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2184.2004.00297.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v10.i22.3308"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1067\/msy.2002.125785"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.34225a"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-02-0572"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000128326.95294.14"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64039-4"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.22650"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.6.1703"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1995.6.8-1029"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2005.01098.x"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.4.652"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3985"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215182"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.21-1-98"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5417.1168"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510310135"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/81326"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.9124"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvg173"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.1266"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v9.i6.1287"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.9.1347"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i22.3431"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2003.09.015"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20452"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200500018"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.10.026"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1089\/153623002321025014"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17902"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2004.06.012"}],"container-title":["The 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