{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T11:43:54Z","timestamp":1762083834907,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS Fostering Joint International Research (B)","award":["JP20KK0112","43019NM","JP17H03472","22K18921"],"award-info":[{"award-number":["JP20KK0112","43019NM","JP17H03472","22K18921"]}]},{"name":"JSPS Bilateral Joint Research Projects","award":["JP20KK0112","43019NM","JP17H03472","22K18921"],"award-info":[{"award-number":["JP20KK0112","43019NM","JP17H03472","22K18921"]}]},{"name":"JSPS Grant-in-Aid for Scientific Research (B)","award":["JP20KK0112","43019NM","JP17H03472","22K18921"],"award-info":[{"award-number":["JP20KK0112","43019NM","JP17H03472","22K18921"]}]},{"name":"Grant-in-Aid for Challenging Exploratory Research","award":["JP20KK0112","43019NM","JP17H03472","22K18921"],"award-info":[{"award-number":["JP20KK0112","43019NM","JP17H03472","22K18921"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Human-hepatoblastoma-derived cell line, HepG2, has been widely used in liver and liver cancer studies. HepG2 spheroids produced in a three-dimensional (3D) culture system provide a better biological model than cells cultured in a two-dimensional (2D) culture system. Since cells at the center of spheroids exhibit specific behaviors attributed to hypoxic conditions, a 3D cell culture system that allows the observation of such cells using conventional optical or fluorescence microscopes would be useful. In this study, HepG2 cells were cultured in \u201cCell Dome\u201d, a micro-dome in which cells are enclosed in a cavity consisting of a hemispherical hydrogel shell. HepG2 cells formed hemispherical cell aggregates which filled the cavity of Cell Domes on 18 days of culture and the cells could continue to be cultured for 29 days. The cells at the center of hemispherical cell aggregates were observed using a fluorescence microscope. The cells grew in Cell Domes for 18 days exhibited higher Pi-class Glutathione S-Transferase enzymatic activity, hypoxia inducible factor-1\u03b1 gene expression, and higher tolerance to mitomycin C than those cultured in 2D on tissue culture dishes (* p &lt; 0.05). These results indicate that the center of the glass adhesive surface of hemispherical cell aggregates which is expected to have the similar environment as the center of the spheroids can be directly observed through glass plates. In conclusion, Cell Dome would be useful as an evaluation platform for organized HepG2 cells.<\/jats:p>","DOI":"10.3390\/cells12010069","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T07:30:06Z","timestamp":1672126206000},"page":"69","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cell Dome as an Evaluation Platform for Organized HepG2 Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Ryotaro","family":"Kazama","sequence":"first","affiliation":[{"name":"Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, Toyonaka 560-8531, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1139-7002","authenticated-orcid":false,"given":"Satoshi","family":"Fujita","sequence":"additional","affiliation":[{"name":"AIST-Osaka University Advanced Photonics and Biosensing Open Innovation Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-4798","authenticated-orcid":false,"given":"Shinji","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, Toyonaka 560-8531, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s00204-017-2079-6","article-title":"Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells","volume":"92","author":"Ramirez","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cld.2016.08.001","article-title":"Drug Metabolism in the Liver","volume":"21","author":"Almazroo","year":"2017","journal-title":"Clin. Liver Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.tox.2015.03.002","article-title":"Trovafloxacin-induced replication stress sensitizes HepG2 cells to tumor necrosis factor-alpha-induced cytotoxicity mediated by extracellular signal-regulated kinase and ataxia telangiectasia and Rad3-related","volume":"331","author":"Beggs","year":"2015","journal-title":"Toxicology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1002\/jat.3170","article-title":"Toxicogenomic responses of human liver HepG2 cells to silver nanoparticles","volume":"35","author":"Sahu","year":"2015","journal-title":"J. Appl. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mizoi, K., Arakawa, H., Yano, K., Koyama, S., Kojima, H., and Ogihara, T. (2020). Utility of Three-Dimensional Cultures of Primary Human Hepatocytes (Spheroids) as Pharmacokinetic Models. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100374"},{"key":"ref_6","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":"Lauschke","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-1-4939-2074-7_5","article-title":"Culture and Functional Characterization of Human Hepatoma HepG2 Cells","volume":"1250","author":"Donato","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nii, T., Makino, K., and Tabata, Y. (2020). Three-Dimensional Culture System of Cancer Cells Combined with Biomaterials for Drug Screening. Cancers, 12.","DOI":"10.3390\/cancers12102754"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/j.1469-7580.2007.00778.x","article-title":"Culture of HepG2 liver cells on three dimensional polystyrene scaffolds enhances cell structure and function during toxicological challenge","volume":"211","author":"Bokhari","year":"2007","journal-title":"J. Anat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.4252\/wjsc.v11.i12.1065","article-title":"Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling","volume":"11","author":"Chaicharoenaudomrung","year":"2019","journal-title":"World J. Stem Cells"},{"key":"ref_11","first-page":"1083","article-title":"A 3D in vitro model of differentiated HepG2 cell spheroids with improved liver-like properties for repeated dose high-throughput toxicity studies","volume":"88","author":"Ramaiahgari","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1254\/jphs.13135FP","article-title":"Evaluation of three-dimensional cultured HepG2 cells in a nano culture plate system: An in vitro human model of acetaminophen hepatotoxicity","volume":"124","author":"Aritomi","year":"2014","journal-title":"J. Pharmacol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1093\/abbs\/gmab046","article-title":"Advances in 3D cell culture for liver preclinical studies","volume":"53","author":"Yao","year":"2021","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1124\/dmd.31.8.1035","article-title":"Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties","volume":"31","author":"Wilkening","year":"2003","journal-title":"Drug Metab. Dispos."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1263\/jbb.106.237","article-title":"Micropatterned organoid culture of rat hepatocytes and HepG2 cells","volume":"106","author":"Mori","year":"2008","journal-title":"J. Biosci. Bioeng."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.snb.2019.04.121","article-title":"A microfluidic platform for multi-size 3D tumor culture, monitoring and drug resistance testing","volume":"292","author":"Liu","year":"2019","journal-title":"Sens. Actuators B Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.tiv.2018.02.013","article-title":"Characterization and reproducibility of HepG2 hanging drop spheroids toxicology in vitro","volume":"50","author":"Hurrell","year":"2018","journal-title":"Toxicol. Vitr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5937","DOI":"10.1016\/j.biomaterials.2009.07.031","article-title":"Enzymatically fabricated and degradable microcapsules for production of multicellular spheroids with well-defined diameters of less than 150 \u00b5m","volume":"30","author":"Sakai","year":"2009","journal-title":"Biomaterials"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"43107","DOI":"10.1002\/app.43107","article-title":"Production of hyaluronic-acid-based cell-enclosing microparticles and microcapsules via enzymatic reaction using a microfluidic system","volume":"133","author":"Khanmohammadi","year":"2016","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1002\/jbm.b.34669","article-title":"Engineering HepG2 spheroids with injectable fiber fragments as predictable models for drug metabolism and tumor infiltration","volume":"108","author":"Wei","year":"2020","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"188553","DOI":"10.1016\/j.bbcan.2021.188553","article-title":"Oxygen gradient and tumor heterogeneity: The chronicle of a toxic relationship","volume":"1876","author":"Pandkar","year":"2021","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.drup.2011.03.001","article-title":"Hypoxia-mediated drug resistance: Novel insights on the functional interaction of HIFs and cell death pathways","volume":"14","author":"Rohwer","year":"2011","journal-title":"Drug Resist. Updates"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wrzesinski, K., Rogowska-Wrzesinska, A., Kanlaya, R., Borkowski, K., Schwammle, V., Dai, J., Joensen, K.E., Wojdyla, K., Carvalho, V.B., and Fey, S.J. (2014). The cultural divide: Exponential growth in classical 2D and metabolic equilibrium in 3D environments. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106973"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1517\/14712598.2012.707181","article-title":"Advances in the formation, use and understanding of multi-cellular spheroids","volume":"12","author":"Achilli","year":"2012","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"015002","DOI":"10.1088\/1758-5090\/ac95ce","article-title":"Development of non-adherent cell-enclosing domes with enzymatically cross-linked hydrogel shell","volume":"15","author":"Kazama","year":"2023","journal-title":"Biofabrication"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3622","DOI":"10.1021\/bi300194f","article-title":"Recognition of heteropolysaccharide alginate by periplasmic solute-binding proteins of a bacterial ABC transporter","volume":"51","author":"Nishitani","year":"2012","journal-title":"Biochemistry"},{"key":"ref_27","first-page":"046602","article-title":"Fluorescence studies on nyctinasty which suggest the existence of genus-specific receptors for leaf-movement factor","volume":"76","author":"Nagano","year":"2013","journal-title":"Rep. Prog. Phys."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.actbio.2006.12.002","article-title":"Synthesis and characterization of both ionically and enzymatically cross-linkable alginate","volume":"3","author":"Sakai","year":"2007","journal-title":"Acta Biomater."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6616","DOI":"10.1016\/j.actbio.2013.01.037","article-title":"Impact of the composition of alginate and gelatin derivatives in bioconjugated hydrogels on the fabrication of cell sheets and spherical tissues with living cell sheaths","volume":"9","author":"Liu","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"046602","DOI":"10.1088\/0034-4885\/76\/4\/046602","article-title":"Anomalous transport in the crowded world of biological cells","volume":"76","author":"Hofling","year":"2013","journal-title":"Rep. Prog. Phys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.jbiosc.2013.05.034","article-title":"Preparation of stripe-patterned heterogeneous hydrogel sheets using microfluidic devices for high-density coculture of hepatocytes and fibroblasts","volume":"116","author":"Kobayashi","year":"2013","journal-title":"J. Biosci. Bioeng."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1177\/1534735416670987","article-title":"Houttuynia cordata Thunb Promotes Activation of HIF-1A-FOXO3 and MEF2A Pathways to Induce Apoptosis in Human HepG2 Hepatocellular Carcinoma Cells","volume":"16","author":"Kim","year":"2017","journal-title":"Integr. Cancer Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jbiotec.2010.01.012","article-title":"Multicellular tumor spheroids: An underestimated tool is catching up again","volume":"148","author":"Hirschhaeuser","year":"2010","journal-title":"J. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4111","DOI":"10.1021\/pr0700596","article-title":"Proteomic analysis reveals differences in protein expression in spheroid versus monolayer cultures of low-passage colon carcinoma cells","volume":"6","author":"Gaedtke","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s12935-020-01719-5","article-title":"The role of hypoxia in the tumor microenvironment and development of cancer stem cell: A novel approach to developing treatment","volume":"21","author":"Najafgholian","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2147\/HP.S93413","article-title":"The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy","volume":"3","author":"Muz","year":"2015","journal-title":"Hypoxia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1517\/17425251003674356","article-title":"Three-dimensional culture of hepatocytes for prediction of drug-induced hepatotoxicity","volume":"6","author":"Meng","year":"2010","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1080\/10408444.2020.1756219","article-title":"Three-dimensional liver models: State of the art and their application for hepatotoxicity evaluation","volume":"50","author":"Zhang","year":"2020","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.drudis.2012.10.003","article-title":"Three-dimensional cell culture: The missing link in drug discovery","volume":"18","author":"Breslin","year":"2013","journal-title":"Drug. Discov. Today"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/bit.10655","article-title":"Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types","volume":"83","author":"Kelm","year":"2003","journal-title":"Biotechnol. Bioeng."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"115279","DOI":"10.1016\/j.taap.2020.115279","article-title":"HepG2 (C3A) spheroids show higher sensitivity compared to HepaRG spheroids for drug-induced liver injury (DILI)","volume":"408","author":"Basharat","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4863","DOI":"10.1038\/s41598-019-41273-3","article-title":"Effect of Spheroidal Age on Sorafenib Diffusivity and Toxicity in a 3D HepG2 Spheroid Model","volume":"9","author":"Eilenberger","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1021\/acsomega.1c06302","article-title":"Fabrication of Size-Controllable and Arrangement-Orderly HepG2 Spheroids for Drug Screening via Decellularized Liver Matrix-Derived Micropattern Array Chips","volume":"7","author":"Zhu","year":"2022","journal-title":"ACS Omega"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.biomaterials.2005.07.031","article-title":"Novel hepatocyte culture system developed using microfabrication and collagen\/polyethylene glycol microcontact printing","volume":"27","author":"Fukuda","year":"2006","journal-title":"Biomaterials"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"153","DOI":"10.18063\/IJB.2016.02.002.","article-title":"The development of cell-adhesive hydrogel for 3D printing","volume":"2","author":"Arai","year":"2016","journal-title":"Int. J. Bioprinting"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1021\/bm070300+","article-title":"Peroxidase-catalyzed cell encapsulation in subsieve-size capsules of alginate with phenol moieties in water-immiscible fluid dissolving H2O2","volume":"8","author":"Sakai","year":"2007","journal-title":"Biomacromolecules"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"045007","DOI":"10.1088\/1758-5090\/aadc9e","article-title":"Peroxidase-catalyzed microextrusion bioprinting of cell-laden hydrogel constructs in vaporized ppm-level hydrogen peroxide","volume":"10","author":"Sakai","year":"2018","journal-title":"Biofabrication"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100078","DOI":"10.1016\/j.mtbio.2020.100078","article-title":"Silk fibroin nanofibers: A promising ink additive for extrusion three-dimensional bioprinting","volume":"8","author":"Sakai","year":"2020","journal-title":"Mater. Today Bio."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1002\/mabi.200600069","article-title":"Alginate hydrogels as biomaterials","volume":"6","author":"Augst","year":"2006","journal-title":"Macromol. Biosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1039\/B812086B","article-title":"Novel chitosan derivative soluble at neutral pH and in-situ gellable via peroxidase-catalyzed enzymatic reaction","volume":"19","author":"Sakai","year":"2009","journal-title":"J. Mater. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.tiv.2018.01.023","article-title":"Impact of cell types and culture methods on the functionality of in vitro liver systems\u2014A review of cell systems for hepatotoxicity assessment","volume":"48","author":"Kyffin","year":"2018","journal-title":"Toxicol. In Vitro"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1080\/21691401.2018.1544142","article-title":"The study of establishment of an in vivo tumor model by three-dimensional cells culture systems methods and evaluation of antitumor effect of biotin-conjugated pullulan acetate nanoparticles","volume":"47","author":"Chen","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_53","first-page":"196","article-title":"A 3D bioprinting liver umor model for drug screening","volume":"5","author":"Xinwei","year":"2016","journal-title":"World J. Pharm. Pharm. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8122","DOI":"10.1039\/C9CC03064F","article-title":"A highly selective fluorogenic substrate for imaging glutathione S-transferase P1: Development and cellular applicability in epigenetic studies","volume":"55","author":"Mori","year":"2019","journal-title":"Chem. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev.pharmtox.45.120403.095857","article-title":"Glutathione transferases","volume":"45","author":"Hayes","year":"2005","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2133\/dmpk.DMPK-13-RG-105","article-title":"Evaluation of human hepatocytes cultured by three-dimensional spheroid systems for drug metabolism","volume":"29","author":"Ohkura","year":"2014","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7462","DOI":"10.1021\/acsabm.0c00679","article-title":"One-Step Dip-Coating-Fabricated Core-Shell Silk Fibroin Rice Paper Fibrous Scaffolds for 3D Tumor Spheroid Formation","volume":"3","author":"Fu","year":"2020","journal-title":"ACS Appl. Bio. Mater."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.biopha.2018.02.055","article-title":"Quercetin enhances chemotherapeutic effect of doxorubicin against human breast cancer cells while reducing toxic side effects of it","volume":"100","author":"Li","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_59","first-page":"1","article-title":"Human ABCG2: Structure, function, and its role in multidrug resistance","volume":"3","author":"Mo","year":"2012","journal-title":"Int. J. Biochem. Mol. Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/1\/69\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:49:37Z","timestamp":1760147377000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/1\/69"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,23]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["cells12010069"],"URL":"https:\/\/doi.org\/10.3390\/cells12010069","relation":{},"ISSN":["2073-4409"],"issn-type":[{"type":"electronic","value":"2073-4409"}],"subject":[],"published":{"date-parts":[[2022,12,23]]}}}