{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:19:42Z","timestamp":1772637582537,"version":"3.50.1"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Industrial Core Technology Development Program","award":["10033594"],"award-info":[{"award-number":["10033594"]}]},{"name":"Ministry of Knowledge Economy, Republic of Korea"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Regulatory Toxicology and Pharmacology"],"published-print":{"date-parts":[[2016,11]]},"DOI":"10.1016\/j.yrtph.2016.09.029","type":"journal-article","created":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T04:41:53Z","timestamp":1475296913000},"page":"437-447","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":40,"special_numbering":"C","title":["Human umbilical cord-derived mesenchymal stem cells in acute liver injury: Hepatoprotective efficacy, subchronic toxicity, tumorigenicity, and biodistribution"],"prefix":"10.1016","volume":"81","author":[{"given":"Jun-Won","family":"Yun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Hun","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Euna","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ja-June","family":"Jang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo Ho","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0514-5132","authenticated-orcid":false,"given":"Ji Hyang","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su-youne","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Tac","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Hoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wookhwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Yup","family":"Ku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung-Rok","family":"Do","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byeong-Cheol","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.yrtph.2016.09.029_bib1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.tice.2013.12.006","article-title":"Valproic acid promotes differentiation of hepatocyte-like cells from whole human umbilical cord-derived mesenchymal stem cells","volume":"46","author":"An","year":"2014","journal-title":"Tissue Cell"},{"key":"10.1016\/j.yrtph.2016.09.029_bib2","first-page":"166","article-title":"Antioxidant effects of bone marrow mesenchymal stem cell against carbon tetrachloride-induced oxidative damage in rat livers","volume":"5","author":"Ayatollahi","year":"2014","journal-title":"Int. J. Organ Transpl. Med."},{"key":"10.1016\/j.yrtph.2016.09.029_bib3","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3109\/15563659309000383","article-title":"Role of free radicals in toxic hepatic injury. I. Free radical biochemistry","volume":"31","author":"Brent","year":"1993","journal-title":"J.\u00a0Toxicol. Clin. Toxicol."},{"key":"10.1016\/j.yrtph.2016.09.029_bib4","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.jcyt.2014.07.003","article-title":"Human bone marrow, umbilical cord or liver mesenchymal stromal cells fail to improve liver function in a model of CCl4-induced liver damage in NOD\/SCID\/IL-2R\u03b3(null) mice","volume":"16","author":"Briquet","year":"2014","journal-title":"Cytotherapy"},{"key":"10.1016\/j.yrtph.2016.09.029_bib5","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/1471-230X-12-88","article-title":"Systemic administration of a novel human umbilical cord mesenchymal stem cells population accelerates the resolution of acute liver injury","volume":"12","author":"Burra","year":"2012","journal-title":"BMC Gastroenterol."},{"key":"10.1016\/j.yrtph.2016.09.029_bib6","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/01.TP.0000128326.95294.14","article-title":"Systemic infusion of FLK1(+) mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice","volume":"78","author":"Fang","year":"2004","journal-title":"Transplantation"},{"key":"10.1016\/j.yrtph.2016.09.029_bib7","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s10592-007-9364-5","article-title":"Species-specific mitochondrial DNA markers for identification of non-invasive samples from sympatric carnivores in the Iberian Peninsula","volume":"9","author":"Fernandes","year":"2008","journal-title":"Conserv. Genet."},{"key":"10.1016\/j.yrtph.2016.09.029_bib8","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1089\/scd.2008.0253","article-title":"Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect","volume":"18","author":"Fischer","year":"2009","journal-title":"Stem Cells Dev."},{"key":"10.1016\/j.yrtph.2016.09.029_bib9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000047856","article-title":"The dynamic in\u00a0vivo distribution of bone marrow-derived mesenchymal stem cells after infusion","volume":"169","author":"Gao","year":"2001","journal-title":"Cells Tissues Organs"},{"key":"10.1016\/j.yrtph.2016.09.029_bib10","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/S0091-679X(06)80040-3","article-title":"Appendix 1. Basic properties of mitochondria","volume":"80","author":"Garc\u00eda-Rodr\u00edguez","year":"2007","journal-title":"Methods Cell Biol."},{"key":"10.1016\/j.yrtph.2016.09.029_bib11","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s00216-011-4797-6","article-title":"Multienzyme-modified biosensing surface for the electrochemical analysis of aspartate transaminase and alanine transaminase in human plasma","volume":"400","author":"Han","year":"2011","journal-title":"Anal. Bioanal. Chem."},{"key":"10.1016\/j.yrtph.2016.09.029_bib12","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature06188","article-title":"Mesenchymal stem cells within tumour stroma promote breast cancer metastasis","volume":"449","author":"Karnoub","year":"2007","journal-title":"Nature"},{"key":"10.1016\/j.yrtph.2016.09.029_bib13","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1084\/jem.20051921","article-title":"Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma","volume":"203","author":"Khakoo","year":"2006","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.yrtph.2016.09.029_bib14","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1089\/ten.tea.2013.0073","article-title":"Ex\u00a0vivo expansion of hematopoietic stem- and progenitor cells from cord blood in coculture with mesenchymal stroma cells from amnion, chorion, Wharton's jelly, amniotic fluid, cord blood, and bone marrow","volume":"19","author":"Klein","year":"2013","journal-title":"Tissue Eng. Part A"},{"key":"10.1016\/j.yrtph.2016.09.029_bib15","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1053\/j.gastro.2008.03.015","article-title":"Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells","volume":"134","author":"Kuo","year":"2008","journal-title":"Gastroenterology"},{"key":"10.1016\/j.yrtph.2016.09.029_bib16","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1159\/000080341","article-title":"Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue","volume":"14","author":"Lee","year":"2004","journal-title":"Cell Physiol. Biochem."},{"key":"10.1016\/j.yrtph.2016.09.029_bib17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.stem.2009.05.003","article-title":"Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6","volume":"5","author":"Lee","year":"2009","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.yrtph.2016.09.029_bib18","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/jcmm.12482","article-title":"The multiple functional roles of mesenchymal stem cells in participating in treating liver diseases","volume":"19","author":"Liu","year":"2015","journal-title":"J.\u00a0Cell Mol. Med."},{"key":"10.1016\/j.yrtph.2016.09.029_bib19","doi-asserted-by":"crossref","first-page":"17762","DOI":"10.1038\/srep17762","article-title":"Contribution and Mobilization of Mesenchymal Stem Cells in a mouse model of carbon tetrachloride-induced liver fibrosis","volume":"5","author":"Liu","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.yrtph.2016.09.029_bib20","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.yexcr.2011.12.002","article-title":"Long-term in-vivo tumorigenic assessment of human culture-expanded adipose stromal\/stem cells","volume":"318","author":"MacIsaac","year":"2012","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.yrtph.2016.09.029_bib21","doi-asserted-by":"crossref","first-page":"R593","DOI":"10.1186\/bcr915","article-title":"Chromogenic in situ hybridization (CISH): a novel alternative in screening archival breast cancer tissue samples for HER-2\/neu status","volume":"6","author":"Madrid","year":"2004","journal-title":"Breast Cancer Res."},{"key":"10.1016\/j.yrtph.2016.09.029_bib22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1080\/14653240310000038","article-title":"Quantifying levels of transplanted murine and human mesenchymal stem cells in\u00a0vivo by real-time PCR","volume":"5","author":"McBride","year":"2003","journal-title":"Cytotherapy"},{"key":"10.1016\/j.yrtph.2016.09.029_bib23","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.2165\/00003495-200565170-00003","article-title":"Pathophysiological basis for antioxidant therapy in chronic liver disease","volume":"65","author":"Medina","year":"2005","journal-title":"Drugs"},{"key":"10.1016\/j.yrtph.2016.09.029_bib24","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1634\/stemcells.2006-0243","article-title":"In\u00a0vivo distribution of human adipose-derived mesenchymal stem cells in novel xenotransplantation models","volume":"25","author":"Meyerrose","year":"2007","journal-title":"Stem Cells"},{"key":"10.1016\/j.yrtph.2016.09.029_bib25","series-title":"Good Laboratory Practice Regulation for Non-clinical Laboratory Studies","author":"Ministry of Food and Drug Safety (MFDS)","year":"2005"},{"key":"10.1016\/j.yrtph.2016.09.029_bib26","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jep.2007.02.011","article-title":"Acute and chronic toxicity of the aqueous extract of Artemisia afra in rodents","volume":"112","author":"Mukinda","year":"2007","journal-title":"J.\u00a0Ethnopharmacol."},{"key":"10.1016\/j.yrtph.2016.09.029_bib27","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/jat.2550100408","article-title":"Prevention by silymarin of membrane alterations in acute CCl4 liver damage","volume":"10","author":"Muriel","year":"1990","journal-title":"J.\u00a0Appl. Toxicol."},{"key":"10.1016\/j.yrtph.2016.09.029_bib28","doi-asserted-by":"crossref","first-page":"195","DOI":"10.4252\/wjsc.v6.i2.195","article-title":"Umbilical cord-derived mesenchymal stem cells: their advantages and potential clinical utility","volume":"6","author":"Nagamura-Inoue","year":"2014","journal-title":"World J. Stem Cells"},{"key":"10.1016\/j.yrtph.2016.09.029_bib29","series-title":"Guide for the Care and Use of Laboratory Animals","author":"NRC","year":"2010"},{"key":"10.1016\/j.yrtph.2016.09.029_bib30","series-title":"OECD Guideline for Testing of Chemicals, Test No.408: Repeated Dose 90-day Oral Toxicity Study in Rodents","author":"OECD","year":"1998"},{"key":"10.1016\/j.yrtph.2016.09.029_bib32","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.bbrc.2007.05.150","article-title":"Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells","volume":"363","author":"Parekkadan","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.yrtph.2016.09.029_bib33","doi-asserted-by":"crossref","first-page":"e941","DOI":"10.1371\/journal.pone.0000941","article-title":"Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure","volume":"2","author":"Parekkadan","year":"2007","journal-title":"PLoS One"},{"key":"10.1016\/j.yrtph.2016.09.029_bib34","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"10.1016\/j.yrtph.2016.09.029_bib35","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1089\/scd.2010.0466","article-title":"Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans","volume":"20","author":"Ra","year":"2011","journal-title":"Stem Cells Dev."},{"key":"10.1016\/j.yrtph.2016.09.029_bib36","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1634\/stemcells.21-1-105","article-title":"Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord","volume":"21","author":"Romanov","year":"2003","journal-title":"Stem Cells"},{"key":"10.1016\/j.yrtph.2016.09.029_bib37","first-page":"789526","article-title":"High harvest yield, high expansion, and phenotype stability of CD146 mesenchymal stromal cells from whole primitive human umbilical cord tissue. 2009","volume":"2009","author":"Schugar","year":"2009","journal-title":"J.\u00a0Biomed. Biotechnol."},{"key":"10.1016\/j.yrtph.2016.09.029_bib38","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1634\/stemcells.2007-0381","article-title":"Multipotent stem cells from umbilical cord: cord is richer than blood!","volume":"26","author":"Secco","year":"2008","journal-title":"Stem Cells"},{"key":"10.1016\/j.yrtph.2016.09.029_bib39","doi-asserted-by":"crossref","first-page":"678063","DOI":"10.1155\/2013\/678063","article-title":"Biodistribution of mesenchymal stem\/stromal cells in a preclinical setting","volume":"2013","author":"Senseb\u00e9","year":"2013","journal-title":"Stem Cells Int."},{"key":"10.1016\/j.yrtph.2016.09.029_bib40","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.fct.2009.12.011","article-title":"Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage","volume":"48","author":"Shaker","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.yrtph.2016.09.029_bib41","doi-asserted-by":"crossref","first-page":"725","DOI":"10.5966\/sctm.2012-0034","article-title":"Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients","volume":"1","author":"Shi","year":"2012","journal-title":"Stem Cells Transl. Med."},{"key":"10.1016\/j.yrtph.2016.09.029_bib42","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1002\/stem.1661","article-title":"Concise review: evidence for CD34 as a common marker for diverse progenitors","volume":"32","author":"Sidney","year":"2014","journal-title":"Stem Cells"},{"key":"10.1016\/j.yrtph.2016.09.029_bib43","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.fct.2008.12.022","article-title":"Protective effects of Coriandrum sativum extracts on carbon tetrachloride-induced hepatotoxicity in rats","volume":"47","author":"Sreelatha","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.yrtph.2016.09.029_bib44","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/S0002-9440(10)64785-2","article-title":"Chromogenic in situ hybridization: a practical alternative for fluorescence in situ hybridization to detect HER-2\/neu oncogene amplification in archival breast cancer samples","volume":"157","author":"Tanner","year":"2000","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.yrtph.2016.09.029_bib45","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/(SICI)1099-1573(200005)14:3<160::AID-PTR555>3.0.CO;2-Y","article-title":"Dihydroquercetin as a means of antioxidative defence in rats with tetrachloromethane hepatitis","volume":"14","author":"Teselkin","year":"2000","journal-title":"Phytother. Res."},{"key":"10.1016\/j.yrtph.2016.09.029_bib46","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jcyt.2014.08.009","article-title":"Discarded Wharton jelly of the human umbilical cord: a viable source for mesenchymal stromal cells","volume":"17","author":"Watson","year":"2015","journal-title":"Cytotherapy"},{"key":"10.1016\/j.yrtph.2016.09.029_bib47","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.fct.2007.08.016","article-title":"Protective effects of Pycnogenol on carbon tetrachloride-induced hepatotoxicity in Sprague-Dawley rats","volume":"46","author":"Yang","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.yrtph.2016.09.029_bib48","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1089\/ten.tea.2010.0248","article-title":"Regenerative therapy and cancer: in\u00a0vitro and in\u00a0vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates","volume":"17","author":"Zimmerlin","year":"2011","journal-title":"Tissue Eng. Part A"}],"container-title":["Regulatory Toxicology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S027323001630277X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S027323001630277X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,9,7]],"date-time":"2018-09-07T21:00:50Z","timestamp":1536354050000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S027323001630277X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11]]},"references-count":47,"alternative-id":["S027323001630277X"],"URL":"https:\/\/doi.org\/10.1016\/j.yrtph.2016.09.029","relation":{},"ISSN":["0273-2300"],"issn-type":[{"value":"0273-2300","type":"print"}],"subject":[],"published":{"date-parts":[[2016,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Human umbilical cord-derived mesenchymal stem cells in acute liver injury: Hepatoprotective efficacy, subchronic toxicity, tumorigenicity, and biodistribution","name":"articletitle","label":"Article Title"},{"value":"Regulatory Toxicology and Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.yrtph.2016.09.029","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}