The role of epigenetic modifiers in extended cultures of functional hepatocyte-like cells derived from human neonatal mesenchymal stem cells
The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days...
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| Veröffentlicht in: | Archives of toxicology 2017-06, Vol.91 (6), p.2469-2489 |
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| creator | Cipriano, M. Correia, J. C. Camões, S. P. Oliveira, N. G. Cruz, P. Cruz, H. Castro, M. Ruas, J. L. Santos, J. M. Miranda, J. P. |
| description | The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO). FGF-2 and FGF-4 were also tested to improve endoderm commitment and foregut induction during Step 1 of the differentiation protocol, being
HHEX
expression increased with FGF-2 (4 ng/mL). DMSO (1%, v/v) when added at day 10 enhanced cell morphology, glycogen storage ability, enzymatic activity and induction capacity. Moreover, the stability of the hepatic phenotype under the optimized differentiation conditions was examined up to day 34. Our findings showed that hepatocyte-like cells (HLCs) acquired the ability to metabolize glucose, produce albumin and detoxify ammonia. Global transcriptional analysis of the HLCs showed a partial hepatic differentiation degree. Global analysis of gene expression in the different cells revealed shared expression of gene groups between HLCs and human primary hepatocytes (hpHeps) that were not observed between HepG2 and hpHeps. In addition, bioinformatics analysis of gene expression data placed HLCs between the HepG2 cell line and hpHeps and distant from hnMSCs. The enhanced hepatic differentiation observed was supported by the presence of the hepatic drug transporters OATP-C and MRP-2 and gene expression of the hepatic markers
CK18, TAT, AFP, ALB, HNF4A
and
CEBPA
; and by their ability to display stable UGT-, EROD-, ECOD-, CYP1A1-, CYP2C9- and CYP3A4-dependent activities at levels either comparable with or even higher than those observed in primary hepatocytes and HepG2 cells. Overall, an improvement of the hepatocyte-like phenotype was achieved for an extended culture time suggesting a role of the epigenetic modifiers in hepatic differentiation and maturation and presenting hnMSC-HLCs as an advantageous alternative for drug discovery and in vitro toxicology testing. |
| doi_str_mv | 10.1007/s00204-016-1901-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_500674</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1899720901</sourcerecordid><originalsourceid>FETCH-LOGICAL-c410t-5d86dc99427fc6d9c849d38b34628ff27f81a2dbac17bac20bdf0fb00c190a503</originalsourceid><addsrcrecordid>eNp1kcFu3CAQhlHVqNkkfYBeKqSeaQfsNeZYRW1SKVIv6RnZMGRJbOMCbnffoQ9dVt5EvfQCo-H7f2B-Qt5x-MgB5KcEIKBmwBvGFXC2f0U2vK4EA1m1r8kGqhrYVjb8nFyk9AjARauqN-RcSAVK1nxD_tzvkMYwIA2O4uwfcMLsDR2D9c5jTNRPFPcZJ4uWmmXIS8R0hN0ymezD1A10h3OXgzlkZIN_QmpwGBK1GP2vInIxjHS3jN1EJyx8LooRE05mdxhLnTKOq-SKnLluSPj2tF-SH1-_3F_fsrvvN9-uP98xU3PIbGvbxhqlaiGdaawyba1s1fZV3YjWudJteSds3xkuyyKgtw5cD2DKlLotVJeErb7pN85Lr-foxy4edOi8PrWeSoV6C9DIuvAfVn6O4eeCKevHsMTy86R5q5QUUKZfKL5SJoaUIroXXw76mJde89IlL33MS--L5v3JeelHtC-K54AKIE5PLUfTA8Z_rv6v618NkaS3</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1899720901</pqid></control><display><type>article</type><title>The role of epigenetic modifiers in extended cultures of functional hepatocyte-like cells derived from human neonatal mesenchymal stem cells</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Cipriano, M. ; Correia, J. C. ; Camões, S. P. ; Oliveira, N. G. ; Cruz, P. ; Cruz, H. ; Castro, M. ; Ruas, J. L. ; Santos, J. M. ; Miranda, J. P.</creator><creatorcontrib>Cipriano, M. ; Correia, J. C. ; Camões, S. P. ; Oliveira, N. G. ; Cruz, P. ; Cruz, H. ; Castro, M. ; Ruas, J. L. ; Santos, J. M. ; Miranda, J. P.</creatorcontrib><description>The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO). FGF-2 and FGF-4 were also tested to improve endoderm commitment and foregut induction during Step 1 of the differentiation protocol, being
HHEX
expression increased with FGF-2 (4 ng/mL). DMSO (1%, v/v) when added at day 10 enhanced cell morphology, glycogen storage ability, enzymatic activity and induction capacity. Moreover, the stability of the hepatic phenotype under the optimized differentiation conditions was examined up to day 34. Our findings showed that hepatocyte-like cells (HLCs) acquired the ability to metabolize glucose, produce albumin and detoxify ammonia. Global transcriptional analysis of the HLCs showed a partial hepatic differentiation degree. Global analysis of gene expression in the different cells revealed shared expression of gene groups between HLCs and human primary hepatocytes (hpHeps) that were not observed between HepG2 and hpHeps. In addition, bioinformatics analysis of gene expression data placed HLCs between the HepG2 cell line and hpHeps and distant from hnMSCs. The enhanced hepatic differentiation observed was supported by the presence of the hepatic drug transporters OATP-C and MRP-2 and gene expression of the hepatic markers
CK18, TAT, AFP, ALB, HNF4A
and
CEBPA
; and by their ability to display stable UGT-, EROD-, ECOD-, CYP1A1-, CYP2C9- and CYP3A4-dependent activities at levels either comparable with or even higher than those observed in primary hepatocytes and HepG2 cells. Overall, an improvement of the hepatocyte-like phenotype was achieved for an extended culture time suggesting a role of the epigenetic modifiers in hepatic differentiation and maturation and presenting hnMSC-HLCs as an advantageous alternative for drug discovery and in vitro toxicology testing.</description><identifier>ISSN: 0340-5761</identifier><identifier>EISSN: 1432-0738</identifier><identifier>DOI: 10.1007/s00204-016-1901-x</identifier><identifier>PMID: 27909741</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Albumin ; Ammonia ; Azacitidine - pharmacology ; Azacytidine ; Bioinformatics ; Biomarkers ; Biomedical and Life Sciences ; Biomedicine ; Cell culture ; Cell Culture Techniques ; Cell Differentiation - drug effects ; Cell morphology ; Cytochrome P450 ; Cytology ; Differentiation ; Dimethyl sulfoxide ; Dimethyl Sulfoxide - pharmacology ; Drug discovery ; Drug Evaluation, Preclinical - methods ; Drug screening ; Embryogenesis ; Embryonic growth stage ; Endoderm ; Environmental Health ; Enzymatic activity ; Epigenesis, Genetic - drug effects ; Epigenetics ; Fibroblast growth factor 2 ; Fibroblast growth factor 4 ; Foregut ; Gene expression ; Glycogen ; Hepatocyte nuclear factor 4 ; Hepatocytes ; Hepatocytes - drug effects ; Hepatocytes - metabolism ; Humans ; Hydroxamic Acids - pharmacology ; In vitro methods and tests ; Infant, Newborn ; Liver ; Material requirements planning ; Maturation ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchyme ; Models, Biological ; Neonates ; Occupational Medicine/Industrial Medicine ; Pharmacology/Toxicology ; Protocols ; Stem cells ; Toxicology ; Transcription ; Umbilical cord</subject><ispartof>Archives of toxicology, 2017-06, Vol.91 (6), p.2469-2489</ispartof><rights>Springer-Verlag Berlin Heidelberg 2016</rights><rights>Archives of Toxicology is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-5d86dc99427fc6d9c849d38b34628ff27f81a2dbac17bac20bdf0fb00c190a503</citedby><cites>FETCH-LOGICAL-c410t-5d86dc99427fc6d9c849d38b34628ff27f81a2dbac17bac20bdf0fb00c190a503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00204-016-1901-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00204-016-1901-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,777,781,882,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27909741$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:135835812$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Cipriano, M.</creatorcontrib><creatorcontrib>Correia, J. C.</creatorcontrib><creatorcontrib>Camões, S. P.</creatorcontrib><creatorcontrib>Oliveira, N. G.</creatorcontrib><creatorcontrib>Cruz, P.</creatorcontrib><creatorcontrib>Cruz, H.</creatorcontrib><creatorcontrib>Castro, M.</creatorcontrib><creatorcontrib>Ruas, J. L.</creatorcontrib><creatorcontrib>Santos, J. M.</creatorcontrib><creatorcontrib>Miranda, J. P.</creatorcontrib><title>The role of epigenetic modifiers in extended cultures of functional hepatocyte-like cells derived from human neonatal mesenchymal stem cells</title><title>Archives of toxicology</title><addtitle>Arch Toxicol</addtitle><addtitle>Arch Toxicol</addtitle><description>The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO). FGF-2 and FGF-4 were also tested to improve endoderm commitment and foregut induction during Step 1 of the differentiation protocol, being
HHEX
expression increased with FGF-2 (4 ng/mL). DMSO (1%, v/v) when added at day 10 enhanced cell morphology, glycogen storage ability, enzymatic activity and induction capacity. Moreover, the stability of the hepatic phenotype under the optimized differentiation conditions was examined up to day 34. Our findings showed that hepatocyte-like cells (HLCs) acquired the ability to metabolize glucose, produce albumin and detoxify ammonia. Global transcriptional analysis of the HLCs showed a partial hepatic differentiation degree. Global analysis of gene expression in the different cells revealed shared expression of gene groups between HLCs and human primary hepatocytes (hpHeps) that were not observed between HepG2 and hpHeps. In addition, bioinformatics analysis of gene expression data placed HLCs between the HepG2 cell line and hpHeps and distant from hnMSCs. The enhanced hepatic differentiation observed was supported by the presence of the hepatic drug transporters OATP-C and MRP-2 and gene expression of the hepatic markers
CK18, TAT, AFP, ALB, HNF4A
and
CEBPA
; and by their ability to display stable UGT-, EROD-, ECOD-, CYP1A1-, CYP2C9- and CYP3A4-dependent activities at levels either comparable with or even higher than those observed in primary hepatocytes and HepG2 cells. Overall, an improvement of the hepatocyte-like phenotype was achieved for an extended culture time suggesting a role of the epigenetic modifiers in hepatic differentiation and maturation and presenting hnMSC-HLCs as an advantageous alternative for drug discovery and in vitro toxicology testing.</description><subject>Albumin</subject><subject>Ammonia</subject><subject>Azacitidine - pharmacology</subject><subject>Azacytidine</subject><subject>Bioinformatics</subject><subject>Biomarkers</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell culture</subject><subject>Cell Culture Techniques</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell morphology</subject><subject>Cytochrome P450</subject><subject>Cytology</subject><subject>Differentiation</subject><subject>Dimethyl sulfoxide</subject><subject>Dimethyl Sulfoxide - pharmacology</subject><subject>Drug discovery</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Drug screening</subject><subject>Embryogenesis</subject><subject>Embryonic growth stage</subject><subject>Endoderm</subject><subject>Environmental Health</subject><subject>Enzymatic activity</subject><subject>Epigenesis, Genetic - drug effects</subject><subject>Epigenetics</subject><subject>Fibroblast growth factor 2</subject><subject>Fibroblast growth factor 4</subject><subject>Foregut</subject><subject>Gene expression</subject><subject>Glycogen</subject><subject>Hepatocyte nuclear factor 4</subject><subject>Hepatocytes</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - metabolism</subject><subject>Humans</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>In vitro methods and tests</subject><subject>Infant, Newborn</subject><subject>Liver</subject><subject>Material requirements planning</subject><subject>Maturation</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchyme</subject><subject>Models, Biological</subject><subject>Neonates</subject><subject>Occupational Medicine/Industrial Medicine</subject><subject>Pharmacology/Toxicology</subject><subject>Protocols</subject><subject>Stem cells</subject><subject>Toxicology</subject><subject>Transcription</subject><subject>Umbilical cord</subject><issn>0340-5761</issn><issn>1432-0738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kcFu3CAQhlHVqNkkfYBeKqSeaQfsNeZYRW1SKVIv6RnZMGRJbOMCbnffoQ9dVt5EvfQCo-H7f2B-Qt5x-MgB5KcEIKBmwBvGFXC2f0U2vK4EA1m1r8kGqhrYVjb8nFyk9AjARauqN-RcSAVK1nxD_tzvkMYwIA2O4uwfcMLsDR2D9c5jTNRPFPcZJ4uWmmXIS8R0hN0ymezD1A10h3OXgzlkZIN_QmpwGBK1GP2vInIxjHS3jN1EJyx8LooRE05mdxhLnTKOq-SKnLluSPj2tF-SH1-_3F_fsrvvN9-uP98xU3PIbGvbxhqlaiGdaawyba1s1fZV3YjWudJteSds3xkuyyKgtw5cD2DKlLotVJeErb7pN85Lr-foxy4edOi8PrWeSoV6C9DIuvAfVn6O4eeCKevHsMTy86R5q5QUUKZfKL5SJoaUIroXXw76mJde89IlL33MS--L5v3JeelHtC-K54AKIE5PLUfTA8Z_rv6v618NkaS3</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Cipriano, M.</creator><creator>Correia, J. 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C. ; Camões, S. P. ; Oliveira, N. G. ; Cruz, P. ; Cruz, H. ; Castro, M. ; Ruas, J. L. ; Santos, J. M. ; Miranda, J. P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-5d86dc99427fc6d9c849d38b34628ff27f81a2dbac17bac20bdf0fb00c190a503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Albumin</topic><topic>Ammonia</topic><topic>Azacitidine - pharmacology</topic><topic>Azacytidine</topic><topic>Bioinformatics</topic><topic>Biomarkers</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell culture</topic><topic>Cell Culture Techniques</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell morphology</topic><topic>Cytochrome P450</topic><topic>Cytology</topic><topic>Differentiation</topic><topic>Dimethyl sulfoxide</topic><topic>Dimethyl Sulfoxide - pharmacology</topic><topic>Drug discovery</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Drug screening</topic><topic>Embryogenesis</topic><topic>Embryonic growth stage</topic><topic>Endoderm</topic><topic>Environmental Health</topic><topic>Enzymatic activity</topic><topic>Epigenesis, Genetic - drug effects</topic><topic>Epigenetics</topic><topic>Fibroblast growth factor 2</topic><topic>Fibroblast growth factor 4</topic><topic>Foregut</topic><topic>Gene expression</topic><topic>Glycogen</topic><topic>Hepatocyte nuclear factor 4</topic><topic>Hepatocytes</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - metabolism</topic><topic>Humans</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>In vitro methods and tests</topic><topic>Infant, Newborn</topic><topic>Liver</topic><topic>Material requirements planning</topic><topic>Maturation</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchyme</topic><topic>Models, Biological</topic><topic>Neonates</topic><topic>Occupational Medicine/Industrial Medicine</topic><topic>Pharmacology/Toxicology</topic><topic>Protocols</topic><topic>Stem cells</topic><topic>Toxicology</topic><topic>Transcription</topic><topic>Umbilical cord</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cipriano, M.</creatorcontrib><creatorcontrib>Correia, J. 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C.</au><au>Camões, S. P.</au><au>Oliveira, N. G.</au><au>Cruz, P.</au><au>Cruz, H.</au><au>Castro, M.</au><au>Ruas, J. L.</au><au>Santos, J. M.</au><au>Miranda, J. P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of epigenetic modifiers in extended cultures of functional hepatocyte-like cells derived from human neonatal mesenchymal stem cells</atitle><jtitle>Archives of toxicology</jtitle><stitle>Arch Toxicol</stitle><addtitle>Arch Toxicol</addtitle><date>2017-06-01</date><risdate>2017</risdate><volume>91</volume><issue>6</issue><spage>2469</spage><epage>2489</epage><pages>2469-2489</pages><issn>0340-5761</issn><eissn>1432-0738</eissn><abstract>The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO). FGF-2 and FGF-4 were also tested to improve endoderm commitment and foregut induction during Step 1 of the differentiation protocol, being
HHEX
expression increased with FGF-2 (4 ng/mL). DMSO (1%, v/v) when added at day 10 enhanced cell morphology, glycogen storage ability, enzymatic activity and induction capacity. Moreover, the stability of the hepatic phenotype under the optimized differentiation conditions was examined up to day 34. Our findings showed that hepatocyte-like cells (HLCs) acquired the ability to metabolize glucose, produce albumin and detoxify ammonia. Global transcriptional analysis of the HLCs showed a partial hepatic differentiation degree. Global analysis of gene expression in the different cells revealed shared expression of gene groups between HLCs and human primary hepatocytes (hpHeps) that were not observed between HepG2 and hpHeps. In addition, bioinformatics analysis of gene expression data placed HLCs between the HepG2 cell line and hpHeps and distant from hnMSCs. The enhanced hepatic differentiation observed was supported by the presence of the hepatic drug transporters OATP-C and MRP-2 and gene expression of the hepatic markers
CK18, TAT, AFP, ALB, HNF4A
and
CEBPA
; and by their ability to display stable UGT-, EROD-, ECOD-, CYP1A1-, CYP2C9- and CYP3A4-dependent activities at levels either comparable with or even higher than those observed in primary hepatocytes and HepG2 cells. Overall, an improvement of the hepatocyte-like phenotype was achieved for an extended culture time suggesting a role of the epigenetic modifiers in hepatic differentiation and maturation and presenting hnMSC-HLCs as an advantageous alternative for drug discovery and in vitro toxicology testing.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>27909741</pmid><doi>10.1007/s00204-016-1901-x</doi><tpages>21</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Archives of toxicology, 2017-06, Vol.91 (6), p.2469-2489 |
| issn | 0340-5761 1432-0738 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_500674 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Albumin Ammonia Azacitidine - pharmacology Azacytidine Bioinformatics Biomarkers Biomedical and Life Sciences Biomedicine Cell culture Cell Culture Techniques Cell Differentiation - drug effects Cell morphology Cytochrome P450 Cytology Differentiation Dimethyl sulfoxide Dimethyl Sulfoxide - pharmacology Drug discovery Drug Evaluation, Preclinical - methods Drug screening Embryogenesis Embryonic growth stage Endoderm Environmental Health Enzymatic activity Epigenesis, Genetic - drug effects Epigenetics Fibroblast growth factor 2 Fibroblast growth factor 4 Foregut Gene expression Glycogen Hepatocyte nuclear factor 4 Hepatocytes Hepatocytes - drug effects Hepatocytes - metabolism Humans Hydroxamic Acids - pharmacology In vitro methods and tests Infant, Newborn Liver Material requirements planning Maturation Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchyme Models, Biological Neonates Occupational Medicine/Industrial Medicine Pharmacology/Toxicology Protocols Stem cells Toxicology Transcription Umbilical cord |
| title | The role of epigenetic modifiers in extended cultures of functional hepatocyte-like cells derived from human neonatal mesenchymal stem cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T00%3A43%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20role%20of%20epigenetic%20modifiers%20in%20extended%20cultures%20of%20functional%20hepatocyte-like%20cells%20derived%20from%20human%20neonatal%20mesenchymal%20stem%20cells&rft.jtitle=Archives%20of%20toxicology&rft.au=Cipriano,%20M.&rft.date=2017-06-01&rft.volume=91&rft.issue=6&rft.spage=2469&rft.epage=2489&rft.pages=2469-2489&rft.issn=0340-5761&rft.eissn=1432-0738&rft_id=info:doi/10.1007/s00204-016-1901-x&rft_dat=%3Cproquest_swepu%3E1899720901%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1899720901&rft_id=info:pmid/27909741&rfr_iscdi=true |