Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications
Maintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro...
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| Veröffentlicht in: | Biotechnology and bioengineering 2018-10, Vol.115 (10), p.2585-2594 |
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| creator | Ortega‐Ribera, Martí Fernández‐Iglesias, Anabel Illa, Xavi Moya, Ana Molina, Víctor Maeso‐Díaz, Raquel Fondevila, Constantino Peralta, Carmen Bosch, Jaume Villa, Rosa Gracia‐Sancho, Jordi |
| description | Maintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro based on the main characteristics of the liver sinusoid: unique cellular architecture, endothelial biodynamic stimulation, and parenchymal zonation. Primary hepatocytes and liver sinusoidal endothelial cells (LSEC) were isolated from control and cirrhotic human or control rat livers and cultured in conventional in vitro platforms or within our liver‐resembling device. Hepatocytes phenotype, function, and response to hepatotoxic drugs were analyzed. Results evidenced that mimicking the in vivo sinusoidal environment within our biosystem, primary human and rat hepatocytes cocultured with functional LSEC maintained morphology and showed high albumin and urea production, enhanced cytochrome P450 family 3 subfamily A member 4 (CYP3A4) activity, and maintained expression of hepatocyte nuclear factor 4 alpha (hnf4α) and transporters, showing delayed hepatocyte dedifferentiation. In addition, differentiated hepatocytes cultured within this liver‐resembling device responded to acute treatment with known hepatotoxic drugs significantly different from those seen in conventional culture platforms. In conclusion, this study describes a new bioengineered device that mimics the human sinusoid in vitro, representing a novel method to study liver diseases and toxicology.
A new bioengineered device that mimics the human liver sinusoid is presented. The device represents a new tool for biomedical research on liver disease and toxicology. |
| doi_str_mv | 10.1002/bit.26776 |
| format | Article |
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A new bioengineered device that mimics the human liver sinusoid is presented. The device represents a new tool for biomedical research on liver disease and toxicology.</description><identifier>ISSN: 0006-3592</identifier><identifier>EISSN: 1097-0290</identifier><identifier>DOI: 10.1002/bit.26776</identifier><identifier>PMID: 29940068</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Animals ; Biocompatibility ; Bioengineering ; Biomedical materials ; Capillaries - cytology ; Capillaries - metabolism ; Cell culture ; Coculture Techniques - instrumentation ; Coculture Techniques - methods ; Cytochrome ; Cytochrome P450 ; Cytochromes P450 ; Cèl·lules hepàtiques ; Drug screening ; Drugs ; Endothelial cells ; Endothelial Cells - cytology ; Endothelial Cells - metabolism ; Genotype & phenotype ; hepatocyte ; Hepatocyte nuclear factor 4 ; Hepatocytes ; Hepatocytes - cytology ; Hepatocytes - metabolism ; Humans ; In vitro methods and tests ; Lab-On-A-Chip Devices ; Liver ; Liver - blood supply ; Liver - cytology ; Liver - metabolism ; Liver cells ; Liver diseases ; liver sinusoidal endothelial cells ; liver‐on‐a‐chip ; LSEC ; Malalties del fetge ; Male ; Mimicry ; Morphology ; Phenotypes ; Platforms ; Rats ; Rats, Wistar ; sinusoid ; Support systems ; Toxicology ; Urea ; Zonation</subject><ispartof>Biotechnology and bioengineering, 2018-10, Vol.115 (10), p.2585-2594</ispartof><rights>2018 The Authors. Published by Wiley Periodicals, Inc.</rights><rights>2018 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.</rights><rights>2018 Wiley Periodicals, Inc.</rights><rights>cc-by (c) Ortega et al., 2018 info:eu-repo/semantics/openAccess <a href="http://creativecommons.org/licenses/by/3.0/es/">http://creativecommons.org/licenses/by/3.0/es/</a></rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5226-a0363f2208d83c36585ca0087beae41c8b5b9b169628eb8a5422f3c1908264683</citedby><cites>FETCH-LOGICAL-c5226-a0363f2208d83c36585ca0087beae41c8b5b9b169628eb8a5422f3c1908264683</cites><orcidid>0000-0001-8647-7069 ; 0000-0001-7736-4089</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fbit.26776$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fbit.26776$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1417,26974,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29940068$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ortega‐Ribera, Martí</creatorcontrib><creatorcontrib>Fernández‐Iglesias, Anabel</creatorcontrib><creatorcontrib>Illa, Xavi</creatorcontrib><creatorcontrib>Moya, Ana</creatorcontrib><creatorcontrib>Molina, Víctor</creatorcontrib><creatorcontrib>Maeso‐Díaz, Raquel</creatorcontrib><creatorcontrib>Fondevila, Constantino</creatorcontrib><creatorcontrib>Peralta, Carmen</creatorcontrib><creatorcontrib>Bosch, Jaume</creatorcontrib><creatorcontrib>Villa, Rosa</creatorcontrib><creatorcontrib>Gracia‐Sancho, Jordi</creatorcontrib><title>Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications</title><title>Biotechnology and bioengineering</title><addtitle>Biotechnol Bioeng</addtitle><description>Maintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro based on the main characteristics of the liver sinusoid: unique cellular architecture, endothelial biodynamic stimulation, and parenchymal zonation. Primary hepatocytes and liver sinusoidal endothelial cells (LSEC) were isolated from control and cirrhotic human or control rat livers and cultured in conventional in vitro platforms or within our liver‐resembling device. Hepatocytes phenotype, function, and response to hepatotoxic drugs were analyzed. Results evidenced that mimicking the in vivo sinusoidal environment within our biosystem, primary human and rat hepatocytes cocultured with functional LSEC maintained morphology and showed high albumin and urea production, enhanced cytochrome P450 family 3 subfamily A member 4 (CYP3A4) activity, and maintained expression of hepatocyte nuclear factor 4 alpha (hnf4α) and transporters, showing delayed hepatocyte dedifferentiation. In addition, differentiated hepatocytes cultured within this liver‐resembling device responded to acute treatment with known hepatotoxic drugs significantly different from those seen in conventional culture platforms. In conclusion, this study describes a new bioengineered device that mimics the human sinusoid in vitro, representing a novel method to study liver diseases and toxicology.
A new bioengineered device that mimics the human liver sinusoid is presented. The device represents a new tool for biomedical research on liver disease and toxicology.</description><subject>Animals</subject><subject>Biocompatibility</subject><subject>Bioengineering</subject><subject>Biomedical materials</subject><subject>Capillaries - cytology</subject><subject>Capillaries - metabolism</subject><subject>Cell culture</subject><subject>Coculture Techniques - instrumentation</subject><subject>Coculture Techniques - methods</subject><subject>Cytochrome</subject><subject>Cytochrome P450</subject><subject>Cytochromes P450</subject><subject>Cèl·lules hepàtiques</subject><subject>Drug screening</subject><subject>Drugs</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelial Cells - metabolism</subject><subject>Genotype & phenotype</subject><subject>hepatocyte</subject><subject>Hepatocyte nuclear factor 4</subject><subject>Hepatocytes</subject><subject>Hepatocytes - cytology</subject><subject>Hepatocytes - metabolism</subject><subject>Humans</subject><subject>In vitro methods and tests</subject><subject>Lab-On-A-Chip Devices</subject><subject>Liver</subject><subject>Liver - blood supply</subject><subject>Liver - cytology</subject><subject>Liver - metabolism</subject><subject>Liver cells</subject><subject>Liver diseases</subject><subject>liver sinusoidal endothelial cells</subject><subject>liver‐on‐a‐chip</subject><subject>LSEC</subject><subject>Malalties del fetge</subject><subject>Male</subject><subject>Mimicry</subject><subject>Morphology</subject><subject>Phenotypes</subject><subject>Platforms</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>sinusoid</subject><subject>Support systems</subject><subject>Toxicology</subject><subject>Urea</subject><subject>Zonation</subject><issn>0006-3592</issn><issn>1097-0290</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>XX2</sourceid><recordid>eNp1kU1v1DAQhi1ERZfCgT-ALHHikNYfieNckGgFpVIlJFTOlu1MiEtiBzvZqv8eb7NdtYceLHtmHr8zoxehD5ScUkLYmXHzKRN1LV6hDSVNXRDWkNdoQwgRBa8adozepnSbw1oK8QYds6Ypc01u0N9fkGA0g_YWcOjw3APul1F7PLgtRJycX1JwLXYea9wNi2udxS1sXebv3Nxj48IIOakHrH2Lp17HUVtY5jU1TUN-zC749A4ddXpI8H5_n6Df37_dXPworn9eXl18vS5sxZgoNOGCd4wR2UpuuahkZTUhsjagoaRWmso0hopGMAlG6qpkrOOWNkQyUQrJT9CXVXdaTB7Ngp-jHtQU3ajjvQraqecV73r1J2yVyE1rSbMAXQVsWqyKYCHmFR4-HoLdyTRTvCq53DX9tG8aw78F0qxuwxJ93lMxSvNkNalFpj7vlWNIKUJ3mIoStfNSZS_Vg5eZ_fh0jQP5aF4Gzlbgzg1w_7KSOr-6WSX_A5SGqZg</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Ortega‐Ribera, 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Fernández‐Iglesias, Anabel ; Illa, Xavi ; Moya, Ana ; Molina, Víctor ; Maeso‐Díaz, Raquel ; Fondevila, Constantino ; Peralta, Carmen ; Bosch, Jaume ; Villa, Rosa ; Gracia‐Sancho, Jordi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5226-a0363f2208d83c36585ca0087beae41c8b5b9b169628eb8a5422f3c1908264683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Biocompatibility</topic><topic>Bioengineering</topic><topic>Biomedical materials</topic><topic>Capillaries - cytology</topic><topic>Capillaries - metabolism</topic><topic>Cell culture</topic><topic>Coculture Techniques - instrumentation</topic><topic>Coculture Techniques - methods</topic><topic>Cytochrome</topic><topic>Cytochrome P450</topic><topic>Cytochromes P450</topic><topic>Cèl·lules hepàtiques</topic><topic>Drug screening</topic><topic>Drugs</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelial Cells - metabolism</topic><topic>Genotype & phenotype</topic><topic>hepatocyte</topic><topic>Hepatocyte nuclear factor 4</topic><topic>Hepatocytes</topic><topic>Hepatocytes - cytology</topic><topic>Hepatocytes - metabolism</topic><topic>Humans</topic><topic>In vitro methods and tests</topic><topic>Lab-On-A-Chip Devices</topic><topic>Liver</topic><topic>Liver - blood supply</topic><topic>Liver - cytology</topic><topic>Liver - metabolism</topic><topic>Liver cells</topic><topic>Liver diseases</topic><topic>liver sinusoidal endothelial cells</topic><topic>liver‐on‐a‐chip</topic><topic>LSEC</topic><topic>Malalties del fetge</topic><topic>Male</topic><topic>Mimicry</topic><topic>Morphology</topic><topic>Phenotypes</topic><topic>Platforms</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>sinusoid</topic><topic>Support systems</topic><topic>Toxicology</topic><topic>Urea</topic><topic>Zonation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ortega‐Ribera, Martí</creatorcontrib><creatorcontrib>Fernández‐Iglesias, Anabel</creatorcontrib><creatorcontrib>Illa, Xavi</creatorcontrib><creatorcontrib>Moya, Ana</creatorcontrib><creatorcontrib>Molina, Víctor</creatorcontrib><creatorcontrib>Maeso‐Díaz, Raquel</creatorcontrib><creatorcontrib>Fondevila, Constantino</creatorcontrib><creatorcontrib>Peralta, Carmen</creatorcontrib><creatorcontrib>Bosch, Jaume</creatorcontrib><creatorcontrib>Villa, Rosa</creatorcontrib><creatorcontrib>Gracia‐Sancho, Jordi</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE 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Xavi</au><au>Moya, Ana</au><au>Molina, Víctor</au><au>Maeso‐Díaz, Raquel</au><au>Fondevila, Constantino</au><au>Peralta, Carmen</au><au>Bosch, Jaume</au><au>Villa, Rosa</au><au>Gracia‐Sancho, Jordi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications</atitle><jtitle>Biotechnology and bioengineering</jtitle><addtitle>Biotechnol Bioeng</addtitle><date>2018-10</date><risdate>2018</risdate><volume>115</volume><issue>10</issue><spage>2585</spage><epage>2594</epage><pages>2585-2594</pages><issn>0006-3592</issn><eissn>1097-0290</eissn><abstract>Maintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro based on the main characteristics of the liver sinusoid: unique cellular architecture, endothelial biodynamic stimulation, and parenchymal zonation. Primary hepatocytes and liver sinusoidal endothelial cells (LSEC) were isolated from control and cirrhotic human or control rat livers and cultured in conventional in vitro platforms or within our liver‐resembling device. Hepatocytes phenotype, function, and response to hepatotoxic drugs were analyzed. Results evidenced that mimicking the in vivo sinusoidal environment within our biosystem, primary human and rat hepatocytes cocultured with functional LSEC maintained morphology and showed high albumin and urea production, enhanced cytochrome P450 family 3 subfamily A member 4 (CYP3A4) activity, and maintained expression of hepatocyte nuclear factor 4 alpha (hnf4α) and transporters, showing delayed hepatocyte dedifferentiation. In addition, differentiated hepatocytes cultured within this liver‐resembling device responded to acute treatment with known hepatotoxic drugs significantly different from those seen in conventional culture platforms. In conclusion, this study describes a new bioengineered device that mimics the human sinusoid in vitro, representing a novel method to study liver diseases and toxicology.
A new bioengineered device that mimics the human liver sinusoid is presented. The device represents a new tool for biomedical research on liver disease and toxicology.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29940068</pmid><doi>10.1002/bit.26776</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-8647-7069</orcidid><orcidid>https://orcid.org/0000-0001-7736-4089</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Biotechnology and bioengineering, 2018-10, Vol.115 (10), p.2585-2594 |
| issn | 0006-3592 1097-0290 |
| language | eng |
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| source | MEDLINE; Access via Wiley Online Library; Recercat |
| subjects | Animals Biocompatibility Bioengineering Biomedical materials Capillaries - cytology Capillaries - metabolism Cell culture Coculture Techniques - instrumentation Coculture Techniques - methods Cytochrome Cytochrome P450 Cytochromes P450 Cèl·lules hepàtiques Drug screening Drugs Endothelial cells Endothelial Cells - cytology Endothelial Cells - metabolism Genotype & phenotype hepatocyte Hepatocyte nuclear factor 4 Hepatocytes Hepatocytes - cytology Hepatocytes - metabolism Humans In vitro methods and tests Lab-On-A-Chip Devices Liver Liver - blood supply Liver - cytology Liver - metabolism Liver cells Liver diseases liver sinusoidal endothelial cells liver‐on‐a‐chip LSEC Malalties del fetge Male Mimicry Morphology Phenotypes Platforms Rats Rats, Wistar sinusoid Support systems Toxicology Urea Zonation |
| title | Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications |
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