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Hepatic esterase activity is increased in hepatocyte-like cells derived from human embryonic stem cells using a 3D culture system
Objectives The aim of the study is to generate a spherical three-dimensional (3D) aggregate of hepatocyte-like cells (HLCs) differentiated from human embryonic stem cells and to investigate the effect of the 3D environment on hepatic maturation and drug metabolism. Results Quantitative real-time PCR...
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| Published in: | Biotechnology letters 2018-05, Vol.40 (5), p.755-763 |
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| container_issue | 5 |
| container_start_page | 755 |
| container_title | Biotechnology letters |
| container_volume | 40 |
| creator | Choi, Young-Jun Kim, Hyemin Kim, Ji-Woo Yoon, Seokjoo Park, Han-Jin |
| description | Objectives
The aim of the study is to generate a spherical three-dimensional (3D) aggregate of hepatocyte-like cells (HLCs) differentiated from human embryonic stem cells and to investigate the effect of the 3D environment on hepatic maturation and drug metabolism.
Results
Quantitative real-time PCR analysis indicated that gene expression of mature hepatocyte markers, drug-metabolizing enzymes, and hepatic transporters was significantly higher in HLCs cultured in the 3D system than in those cultured in a two-dimensional system (
p
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| doi_str_mv | 10.1007/s10529-018-2528-1 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2006662803</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2006662803</sourcerecordid><originalsourceid>FETCH-LOGICAL-c409t-2bb97c2e799e85d125287c54b25812182221e36911d7cc6e33408c3e0e67a7413</originalsourceid><addsrcrecordid>eNp1kE1P3DAQhi1UBNuFH8ClstSz2xknseNjRaFUQuICZytxZne95GNrJ0g59p_jaLftqSdbnsfPzLyM3SB8QQD9NSIU0gjAUshClgLP2AoLnQmltfrAVoA5iiI38pJ9jHEPAEaDvmCX0uQqLzSs2O8HOlSjd5ziSKGKxCs3-jc_ztxH7nsXKD026cZ3Czm4eSTR-lfijto28oaCf0vAJgwd301d1XPq6jAPfZImZ3fipuj7La949p27qR2nQDzOS_2KnW-qNtL16Vyzl_u759sH8fj04-ftt0fhcjCjkHVttJOkjaGyaHBZWLsir2VRosRSSomUKYPYaOcUZVkOpcsISOlK55it2eej9xCGX1Na1-6HKfSppZUASilZQpYoPFIuDDEG2thD8F0VZotgl9DtMXSbQrfLDHYxfzqZp7qj5u-PPyknQB6BmEr9lsK_1v-3vgNlY4z3</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2006662803</pqid></control><display><type>article</type><title>Hepatic esterase activity is increased in hepatocyte-like cells derived from human embryonic stem cells using a 3D culture system</title><source>Springer Nature</source><creator>Choi, Young-Jun ; Kim, Hyemin ; Kim, Ji-Woo ; Yoon, Seokjoo ; Park, Han-Jin</creator><creatorcontrib>Choi, Young-Jun ; Kim, Hyemin ; Kim, Ji-Woo ; Yoon, Seokjoo ; Park, Han-Jin</creatorcontrib><description>Objectives
The aim of the study is to generate a spherical three-dimensional (3D) aggregate of hepatocyte-like cells (HLCs) differentiated from human embryonic stem cells and to investigate the effect of the 3D environment on hepatic maturation and drug metabolism.
Results
Quantitative real-time PCR analysis indicated that gene expression of mature hepatocyte markers, drug-metabolizing enzymes, and hepatic transporters was significantly higher in HLCs cultured in the 3D system than in those cultured in a two-dimensional system (
p
< 0.001). Moreover, hepatocyte-specific functions, including albumin secretion and bile canaliculi formation, were increased in HLCs cultured in the 3D system. In particular, 3D spheroidal culture increased expression of
CES1
and
BCHE
, which encode hepatic esterases (
p
< 0.001). The enhanced activities of these hepatic esterases were confirmed by the cholinesterase activity assay and the increased susceptibility of HLCs to oseltamivir, which is metabolized by CES1.
Conclusions
3D spheroidal culture enhances the maturation and drug metabolism of stem cell-derived HLCs, and this may help to optimize hepatic differentiation protocols for hepatotoxicity testing.</description><identifier>ISSN: 0141-5492</identifier><identifier>EISSN: 1573-6776</identifier><identifier>DOI: 10.1007/s10529-018-2528-1</identifier><identifier>PMID: 29464570</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Applied Microbiology ; Bile ducts ; Biochemistry ; Biomedical and Life Sciences ; Biotechnology ; Butyrylcholinesterase - genetics ; Carboxylic Ester Hydrolases - genetics ; Cell culture ; Cell Culture Techniques - methods ; Cell Differentiation - drug effects ; Cells, Cultured ; Cholinesterase ; Drug metabolism ; Embryo cells ; Embryos ; Esterase ; Esterases ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Enzymologic - drug effects ; Hepatocytes - cytology ; Hepatocytes - metabolism ; Hepatotoxicity ; Human Embryonic Stem Cells - cytology ; Human Embryonic Stem Cells - metabolism ; Humans ; Life Sciences ; Liver ; Maturation ; Metabolism ; Microbiology ; Original Research Paper ; Oseltamivir ; Oseltamivir - pharmacology ; Secretion ; Spheroids, Cellular - cytology ; Spheroids, Cellular - metabolism ; Stem cells ; Up-Regulation - drug effects</subject><ispartof>Biotechnology letters, 2018-05, Vol.40 (5), p.755-763</ispartof><rights>Springer Science+Business Media B.V., part of Springer Nature 2018</rights><rights>Biotechnology Letters is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-2bb97c2e799e85d125287c54b25812182221e36911d7cc6e33408c3e0e67a7413</citedby><cites>FETCH-LOGICAL-c409t-2bb97c2e799e85d125287c54b25812182221e36911d7cc6e33408c3e0e67a7413</cites><orcidid>0000-0002-0113-4145</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29464570$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Young-Jun</creatorcontrib><creatorcontrib>Kim, Hyemin</creatorcontrib><creatorcontrib>Kim, Ji-Woo</creatorcontrib><creatorcontrib>Yoon, Seokjoo</creatorcontrib><creatorcontrib>Park, Han-Jin</creatorcontrib><title>Hepatic esterase activity is increased in hepatocyte-like cells derived from human embryonic stem cells using a 3D culture system</title><title>Biotechnology letters</title><addtitle>Biotechnol Lett</addtitle><addtitle>Biotechnol Lett</addtitle><description>Objectives
The aim of the study is to generate a spherical three-dimensional (3D) aggregate of hepatocyte-like cells (HLCs) differentiated from human embryonic stem cells and to investigate the effect of the 3D environment on hepatic maturation and drug metabolism.
Results
Quantitative real-time PCR analysis indicated that gene expression of mature hepatocyte markers, drug-metabolizing enzymes, and hepatic transporters was significantly higher in HLCs cultured in the 3D system than in those cultured in a two-dimensional system (
p
< 0.001). Moreover, hepatocyte-specific functions, including albumin secretion and bile canaliculi formation, were increased in HLCs cultured in the 3D system. In particular, 3D spheroidal culture increased expression of
CES1
and
BCHE
, which encode hepatic esterases (
p
< 0.001). The enhanced activities of these hepatic esterases were confirmed by the cholinesterase activity assay and the increased susceptibility of HLCs to oseltamivir, which is metabolized by CES1.
Conclusions
3D spheroidal culture enhances the maturation and drug metabolism of stem cell-derived HLCs, and this may help to optimize hepatic differentiation protocols for hepatotoxicity testing.</description><subject>Applied Microbiology</subject><subject>Bile ducts</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biotechnology</subject><subject>Butyrylcholinesterase - genetics</subject><subject>Carboxylic Ester Hydrolases - genetics</subject><subject>Cell culture</subject><subject>Cell Culture Techniques - methods</subject><subject>Cell Differentiation - drug effects</subject><subject>Cells, Cultured</subject><subject>Cholinesterase</subject><subject>Drug metabolism</subject><subject>Embryo cells</subject><subject>Embryos</subject><subject>Esterase</subject><subject>Esterases</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Hepatocytes - cytology</subject><subject>Hepatocytes - metabolism</subject><subject>Hepatotoxicity</subject><subject>Human Embryonic Stem Cells - cytology</subject><subject>Human Embryonic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Liver</subject><subject>Maturation</subject><subject>Metabolism</subject><subject>Microbiology</subject><subject>Original Research Paper</subject><subject>Oseltamivir</subject><subject>Oseltamivir - pharmacology</subject><subject>Secretion</subject><subject>Spheroids, Cellular - cytology</subject><subject>Spheroids, Cellular - metabolism</subject><subject>Stem cells</subject><subject>Up-Regulation - drug effects</subject><issn>0141-5492</issn><issn>1573-6776</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kE1P3DAQhi1UBNuFH8ClstSz2xknseNjRaFUQuICZytxZne95GNrJ0g59p_jaLftqSdbnsfPzLyM3SB8QQD9NSIU0gjAUshClgLP2AoLnQmltfrAVoA5iiI38pJ9jHEPAEaDvmCX0uQqLzSs2O8HOlSjd5ziSKGKxCs3-jc_ztxH7nsXKD026cZ3Czm4eSTR-lfijto28oaCf0vAJgwd301d1XPq6jAPfZImZ3fipuj7La949p27qR2nQDzOS_2KnW-qNtL16Vyzl_u759sH8fj04-ftt0fhcjCjkHVttJOkjaGyaHBZWLsir2VRosRSSomUKYPYaOcUZVkOpcsISOlK55it2eej9xCGX1Na1-6HKfSppZUASilZQpYoPFIuDDEG2thD8F0VZotgl9DtMXSbQrfLDHYxfzqZp7qj5u-PPyknQB6BmEr9lsK_1v-3vgNlY4z3</recordid><startdate>20180501</startdate><enddate>20180501</enddate><creator>Choi, Young-Jun</creator><creator>Kim, Hyemin</creator><creator>Kim, Ji-Woo</creator><creator>Yoon, Seokjoo</creator><creator>Park, Han-Jin</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QR</scope><scope>7T7</scope><scope>7TB</scope><scope>7U5</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L6V</scope><scope>L7M</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>Q9U</scope><orcidid>https://orcid.org/0000-0002-0113-4145</orcidid></search><sort><creationdate>20180501</creationdate><title>Hepatic esterase activity is increased in hepatocyte-like cells derived from human embryonic stem cells using a 3D culture system</title><author>Choi, Young-Jun ; Kim, Hyemin ; Kim, Ji-Woo ; Yoon, Seokjoo ; Park, Han-Jin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-2bb97c2e799e85d125287c54b25812182221e36911d7cc6e33408c3e0e67a7413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Applied Microbiology</topic><topic>Bile ducts</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biotechnology</topic><topic>Butyrylcholinesterase - genetics</topic><topic>Carboxylic Ester Hydrolases - genetics</topic><topic>Cell culture</topic><topic>Cell Culture Techniques - methods</topic><topic>Cell Differentiation - drug effects</topic><topic>Cells, Cultured</topic><topic>Cholinesterase</topic><topic>Drug metabolism</topic><topic>Embryo cells</topic><topic>Embryos</topic><topic>Esterase</topic><topic>Esterases</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Hepatocytes - cytology</topic><topic>Hepatocytes - metabolism</topic><topic>Hepatotoxicity</topic><topic>Human Embryonic Stem Cells - cytology</topic><topic>Human Embryonic Stem Cells - metabolism</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Liver</topic><topic>Maturation</topic><topic>Metabolism</topic><topic>Microbiology</topic><topic>Original Research Paper</topic><topic>Oseltamivir</topic><topic>Oseltamivir - pharmacology</topic><topic>Secretion</topic><topic>Spheroids, Cellular - cytology</topic><topic>Spheroids, Cellular - metabolism</topic><topic>Stem cells</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Young-Jun</creatorcontrib><creatorcontrib>Kim, Hyemin</creatorcontrib><creatorcontrib>Kim, Ji-Woo</creatorcontrib><creatorcontrib>Yoon, Seokjoo</creatorcontrib><creatorcontrib>Park, Han-Jin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Engineering Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Science Database (ProQuest)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>ProQuest Central Basic</collection><jtitle>Biotechnology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Young-Jun</au><au>Kim, Hyemin</au><au>Kim, Ji-Woo</au><au>Yoon, Seokjoo</au><au>Park, Han-Jin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatic esterase activity is increased in hepatocyte-like cells derived from human embryonic stem cells using a 3D culture system</atitle><jtitle>Biotechnology letters</jtitle><stitle>Biotechnol Lett</stitle><addtitle>Biotechnol Lett</addtitle><date>2018-05-01</date><risdate>2018</risdate><volume>40</volume><issue>5</issue><spage>755</spage><epage>763</epage><pages>755-763</pages><issn>0141-5492</issn><eissn>1573-6776</eissn><abstract>Objectives
The aim of the study is to generate a spherical three-dimensional (3D) aggregate of hepatocyte-like cells (HLCs) differentiated from human embryonic stem cells and to investigate the effect of the 3D environment on hepatic maturation and drug metabolism.
Results
Quantitative real-time PCR analysis indicated that gene expression of mature hepatocyte markers, drug-metabolizing enzymes, and hepatic transporters was significantly higher in HLCs cultured in the 3D system than in those cultured in a two-dimensional system (
p
< 0.001). Moreover, hepatocyte-specific functions, including albumin secretion and bile canaliculi formation, were increased in HLCs cultured in the 3D system. In particular, 3D spheroidal culture increased expression of
CES1
and
BCHE
, which encode hepatic esterases (
p
< 0.001). The enhanced activities of these hepatic esterases were confirmed by the cholinesterase activity assay and the increased susceptibility of HLCs to oseltamivir, which is metabolized by CES1.
Conclusions
3D spheroidal culture enhances the maturation and drug metabolism of stem cell-derived HLCs, and this may help to optimize hepatic differentiation protocols for hepatotoxicity testing.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>29464570</pmid><doi>10.1007/s10529-018-2528-1</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-0113-4145</orcidid></addata></record> |
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| ispartof | Biotechnology letters, 2018-05, Vol.40 (5), p.755-763 |
| issn | 0141-5492 1573-6776 |
| language | eng |
| recordid | cdi_proquest_journals_2006662803 |
| source | Springer Nature |
| subjects | Applied Microbiology Bile ducts Biochemistry Biomedical and Life Sciences Biotechnology Butyrylcholinesterase - genetics Carboxylic Ester Hydrolases - genetics Cell culture Cell Culture Techniques - methods Cell Differentiation - drug effects Cells, Cultured Cholinesterase Drug metabolism Embryo cells Embryos Esterase Esterases Gene expression Gene Expression Profiling Gene Expression Regulation, Enzymologic - drug effects Hepatocytes - cytology Hepatocytes - metabolism Hepatotoxicity Human Embryonic Stem Cells - cytology Human Embryonic Stem Cells - metabolism Humans Life Sciences Liver Maturation Metabolism Microbiology Original Research Paper Oseltamivir Oseltamivir - pharmacology Secretion Spheroids, Cellular - cytology Spheroids, Cellular - metabolism Stem cells Up-Regulation - drug effects |
| title | Hepatic esterase activity is increased in hepatocyte-like cells derived from human embryonic stem cells using a 3D culture system |
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