{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T07:51:38Z","timestamp":1769068298112,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0006309","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T00:00:00Z","timestamp":1522022400000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T00:00:00Z","timestamp":1520985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China (CN)","award":["31401148"],"award-info":[{"award-number":["31401148"]}]},{"name":"National Key Basic Research Program(973 Program) of China","award":["2015CB150300"],"award-info":[{"award-number":["2015CB150300"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31402191"],"award-info":[{"award-number":["31402191"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2011CB965001"],"award-info":[{"award-number":["2011CB965001"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Laboratory Program(CN)","award":["SKLVEB2012KFKT012"],"award-info":[{"award-number":["SKLVEB2012KFKT012"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0006309","type":"journal-article","created":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T17:26:38Z","timestamp":1521048398000},"page":"e0006309","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Three-dimensional hepatocyte culture system for the study of Echinococcus multilocularis larval development"],"prefix":"10.1371","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6467-0247","authenticated-orcid":true,"given":"Li","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yannan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongzi","family":"Lou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianqiu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoquan","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingquan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald P.","family":"McManus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianwu","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanzhong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2018,3,14]]},"reference":[{"issue":"7443","key":"ref1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature12031","article-title":"The genomes of four tapeworm species reveal adaptations to parasitism","volume":"496","author":"IJ Tsai","year":"2013","journal-title":"Nature"},{"issue":"4","key":"ref2","doi-asserted-by":"crossref","first-page":"e0004634","DOI":"10.1371\/journal.pntd.0004634","article-title":"Analysis on gene expression profile in oncospheres and early stage metacestodes from <italic>Echinococcus multilocularis<\/italic>","volume":"10","author":"FQ Huang","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"e722","DOI":"10.1371\/journal.pntd.0000722","article-title":"The global burden of alveolar Echinococcosis","volume":"4","author":"PR Torgerson","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"ref4","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1186\/s13071-016-1687-y","article-title":"<italic>In vitro<\/italic> culture of <italic>Echinococcus multilocularis<\/italic> producing protoscoleces and mouse infection with the cultured vesicles","volume":"9","author":"H Wang","year":"2016","journal-title":"Parasit Vectors"},{"issue":"4","key":"ref5","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.exppara.2008.03.007","article-title":"Recent advances in the <italic>in vitro<\/italic> cultivation and genetic manipulation of <italic>Echinococcus multilocularis<\/italic> metacestodes and germinal cells","volume":"119","author":"K Brehm","year":"2008","journal-title":"Experimental Parasitology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S1471-4922(02)02346-2","article-title":"Culture of <italic>Echinococcus multilocularis<\/italic> metacestodes: an alternative to animal use","volume":"18","author":"A Hemphill","year":"2002","journal-title":"Trends Parasitol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/978-1-59745-204-5_17","article-title":"Axenic in vitro cultivation of <italic>Echinococcus multilocularis<\/italic> metacestode vesicles and the generation of primary cell cultures","volume":"470","author":"M Spiliotis","year":"2009","journal-title":"Methods Mol Biol"},{"issue":"7","key":"ref8","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/pim.12327","article-title":"<italic>In vitro<\/italic> culture of Mesocestoides corti metacestodes and isolation of immunomodulatory excretory-secretory products","volume":"38","author":"E Vendelova","year":"2016","journal-title":"Parasite Immunol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1128\/IAI.64.9.3484-3490.1996","article-title":"Hepatic tissue culture model for study of host-parasite interaction in alveolar echinococcosis","volume":"64","author":"H Jura","year":"1996","journal-title":"Infect Immun"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1517\/17425255.2014.967680","article-title":"Competency of different cell models to predict human hepatotoxic drugs","volume":"10","author":"M J G\u00f3mez-Lech\u00f3n","year":"2014","journal-title":"Expert Opin. Drug. Metab Toxicol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1242\/jcs.00503","article-title":"Modeling tissue-specific signaling and organ function in three-dimensions","volume":"116","author":"KL Schmeichel","year":"2003","journal-title":"J Cell Sci"},{"issue":"5","key":"ref12","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1002\/hep.28780","article-title":"Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation","volume":"64","author":"VM Lauschke","year":"2016","journal-title":"Hepatology"},{"issue":"2","key":"ref13","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.tibtech.2016.08.001","article-title":"Engineered liver platforms for different phases of drug development","volume":"35","author":"BR Ware","year":"2017","journal-title":"Trends Biotechnol"},{"issue":"12","key":"ref14","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1021\/acs.chemrestox.6b00150","article-title":"Novel 3D culture systems for studies of human liver function and assessments of the hepatotoxicity of drugs and drug candidates","volume":"29","author":"VM Lauschke","year":"2016","journal-title":"Chem Res Toxicol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3109\/10408444.2012.682115","article-title":"Organotypic liver culture models: meeting current challenges in toxicity testing","volume":"42","author":"EL Lecluyse","year":"2012","journal-title":"Crit. Rev. Toxicol"},{"issue":"2","key":"ref16","doi-asserted-by":"crossref","first-page":"025022","DOI":"10.1088\/1758-5090\/aa70c7","article-title":"3D liver membrane system by co-culturing human hepatocytes, sinusoidal endothelial and stellate cells","volume":"9","author":"HMM Ahmed","year":"2017","journal-title":"Biofabrication"},{"issue":"6","key":"ref17","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1096\/fj.201601375R","article-title":"Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics","volume":"31","author":"SU Vorrink","year":"2017","journal-title":"FASEB J"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nrmicro2423","article-title":"Organotypic 3D cell culture models: using the rotating wall vessel to study host-pathogen interactions","volume":"8","author":"J Barrila","year":"2010","journal-title":"Nat Rev Microbiol"},{"issue":"4","key":"ref19","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/adt.2014.573","article-title":"Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors","volume":"12","author":"R Edmondson","year":"2014","journal-title":"Assay Drug Dev Technol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/1743-422X-6-103","article-title":"Three-dimensional Huh7 cell culture system for the study of Hepatitis C virus infection","volume":"6","author":"B Sainz Jr","year":"2009","journal-title":"Virol. J"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1016\/j.biomaterials.2013.11.063","article-title":"Molecular mechanisms underlying the enhanced functions of three-dimensional hepatocyte aggregates","volume":"35","author":"TT Chang","year":"2014","journal-title":"Biomaterials"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"e1004381","DOI":"10.1371\/journal.ppat.1004381","article-title":"A new human 3D-liver model unravels the role of galectins in liver infection by the parasite <italic>Entamoeba histolytica<\/italic>","volume":"10","author":"DB Petropolis","year":"2014","journal-title":"PLoS Pathog"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1086\/588819","article-title":"Detection of epithelial-cell injury, and quantification of infection, in the HCT-8 organoid model of cryptosporidiosis","volume":"198","author":"WC Alcantara","year":"2010","journal-title":"J Infect Dis"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/j.biomaterials.2007.11.032","article-title":"The effect of crosslinking heparin to demineralized bone matrix on mechanical strength and specific binding to human bone morphogenetic protein-2","volume":"29","author":"H Lin","year":"2008","journal-title":"Biomaterials"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.2147\/IJN.S75011","article-title":"A hybrid substratum for primary hepatocyte culture that enhances hepatic functionality with low serum dependency","volume":"10","author":"Q Meng","year":"2015","journal-title":"Int J Nanomedicine"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1634\/stemcells.21-5-527","article-title":"Isolation of mouse marrow mesenchymal progenitors by a novel and reliable method","volume":"21","author":"S Sun","year":"2003","journal-title":"Stem Cells"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"6444","DOI":"10.1021\/ac3013708","article-title":"Spatiotemporally controlled and multi-factor involved assay of neuronal compartment regeneration after chemical injury in anintegrated microfluidics","volume":"84","author":"L Li","year":"2012","journal-title":"Anal. Chem"},{"issue":"5","key":"ref28","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1016\/j.biomaterials.2011.10.084","article-title":"Preserved liver-specific functions of hepatocytes in 3D co-culture with endothelial cell sheets","volume":"33","author":"K Kim","year":"2012","journal-title":"Biomaterials"},{"issue":"9","key":"ref29","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1016\/j.biomaterials.2011.12.039","article-title":"Reconstruction of 3D stacked hepatocyte tissues using degradable, microporous poly(d,l-lactide-co- glycolide) membranes","volume":"33","author":"J Kasuya","year":"2012","journal-title":"Biomaterials"},{"issue":"6","key":"ref30","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.jbiosc.2011.01.019","article-title":"Reconstitution of hepatic tissue architectures from fetal liver cells obtained from a three-dimensional culture with a rotating wall vessel bioreactor","volume":"111","author":"M Ishikawa","year":"2011","journal-title":"J Biosci Bioeng"},{"issue":"1","key":"ref31","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0165-2478(03)00162-7","article-title":"Requirement of 3D extracellular network for maintenance of mature hepatocyte morphology and suppression of alpha-fetoprotein synthesis in vitro","volume":"90","author":"EI Kudryavtseva","year":"2003","journal-title":"Immunol Lett"},{"issue":"9","key":"ref32","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.5966\/sctm.2015-0235","article-title":"Functional Maturation of Induced Pluripotent Stem Cell Hepatocytes in Extracellular Matrix-A Comparative Analysis of Bioartificial Liver Microenvironments","volume":"5","author":"B Wang","year":"2016","journal-title":"Stem Cells Transl Med"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"4208","DOI":"10.1016\/j.actbio.2012.06.017","article-title":"Transfection of macrophages by collagen hollow spheres loaded with polyplexes: a step towards modulating inflammation","volume":"8","author":"C Helary","year":"2012","journal-title":"Acta Biomater"},{"issue":"10","key":"ref34","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1039\/c2lc40046d","article-title":"Enhanced bile canaliculi formation enabling direct recovery of biliary metabolites of hepatocytes in 3D collagen gel microcavities","volume":"12","author":"H Matsui","year":"2012","journal-title":"Lab Chip"},{"issue":"29","key":"ref35","doi-asserted-by":"crossref","first-page":"7042","DOI":"10.1016\/j.biomaterials.2011.06.005","article-title":"Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix","volume":"32","author":"R Lang","year":"2011","journal-title":"Biomaterials"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.bbrc.2013.03.008","article-title":"A multicellular 3D heterospheroid model of liver tumor and stromal cells in collagen gel for anti-cancer drug testing","volume":"433","author":"D Yip","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"issue":"23\u201324","key":"ref37","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.1016\/j.biomaterials.2009.03.052","article-title":"The controlled presentation of TGF-beta1 to hepatocytes in a 3D-microfluidic cell culture system","volume":"30","author":"C Zhang","year":"2009","journal-title":"Biomaterials"},{"issue":"5","key":"ref38","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.biomaterials.2011.10.056","article-title":"The enhancement of cancer stem cell properties of MCF-7 cells in 3D collagen scaffolds for modeling of cancer and anti-cancer drugs","volume":"33","author":"L Chen","year":"2012","journal-title":"Biomaterials"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"13724","DOI":"10.1073\/pnas.1008117107","article-title":"Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their anti-inflammatory properties","volume":"107","author":"TJ Bartosh","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2013.01.012","article-title":"A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity","volume":"268","author":"R Kostadinova","year":"2013","journal-title":"Toxicol Appl Pharmacol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/cmi.2010.57","article-title":"Implications of the immunoregulatory functions of mesenchymal stem cells in the treatment of human liver diseases","volume":"8","author":"H Lin","year":"2011","journal-title":"Cell Mol Immunol"},{"issue":"7","key":"ref42","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1002\/term.2099","article-title":"Three-dimensional co-culture of human hepatocytes and mesenchymal stem cells: improved functionality in long-term bioreactor cultures","volume":"11","author":"SP Rebelo","year":"2015","journal-title":"J Tissue Eng Regen Med"},{"key":"ref43","first-page":"1","article-title":"Metabolic oscillations in co-cultures of hepatocytes and mesenchymal stem cells: effects of seeding arrangement and culture mixing","volume":"9999","author":"DA Alzebdeh","year":"2017","journal-title":"J Cell Biochem"},{"issue":"11","key":"ref44","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1089\/ten.tea.2008.0681","article-title":"Long-term superior performance of a stem cell\/hepatocyte device for the treatment of acute liver failure","volume":"15","author":"H Yagi","year":"2009","journal-title":"Tissue Eng Part A"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.toxlet.2013.09.019","article-title":"Alpha-naphthylisothiocyanate modulates hepatobiliary transporters in sandwich-cultured rat hepatocytes","volume":"224","author":"C Guo","year":"2014","journal-title":"Toxicol Lett"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1741-7007-12-5","article-title":"Host insulin stimulates <italic>Echinococcus multilocularis<\/italic> insulin signalling pathways and larval development","volume":"12","author":"S Hemer","year":"2014","journal-title":"BMC Biol"},{"issue":"1","key":"ref47","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/2041-9139-5-10","article-title":"The unique stem cell system of the immortal larva of the human parasite <italic>Echinococcus multilocularis<\/italic>","volume":"5","author":"U Koziol","year":"2014","journal-title":"Evodevo"},{"issue":"2","key":"ref48","doi-asserted-by":"crossref","first-page":"e0005418","DOI":"10.1371\/journal.pntd.0005418","article-title":"EGF-mediated EGFR\/ERK signaling pathway promotes germinative cell proliferation in <italic>Echinococcus multilocularis<\/italic> that contributes to larval growth and development","volume":"11","author":"Z Cheng","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12915-016-0233-x","article-title":"Comparative analysis of Wnt expression identifies a highly conserved developmental transition in flatworms","volume":"14","author":"U Koziol","year":"2016","journal-title":"BMC Biol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.pt.2010.12.012","article-title":"Understanding the laminated layer of larval <italic>Echinococcus<\/italic> I: structure","volume":"27","author":"A D\u00edaz","year":"2011","journal-title":"Trends Parasitol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/bs.apar.2016.09.001","article-title":"<italic>Echinococcus<\/italic>-host interactions at cellular and molecular levels","volume":"95","author":"K Brehm","year":"2017","journal-title":"Adv Parasitol"},{"issue":"8","key":"ref52","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.ijpara.2013.03.006","article-title":"The nervous and prenervous roles of serotonin in <italic>Echinococcus<\/italic> spp","volume":"43","author":"F Camicia","year":"2013","journal-title":"Int J Parasitol"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0006309","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T00:00:00Z","timestamp":1522022400000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0006309","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T08:11:57Z","timestamp":1603959117000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0006309"}},"subtitle":[],"editor":[{"given":"Mara Cecilia","family":"Rosenzvit","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,3,14]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0006309","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0006309","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,14]]}}}