A phenotypic in vitro model for the main determinants of human whole heart function
Abstract This article details the construction and testing of a phenotypic assay system that models in vivo cardiac function in a parallel in vitro environment with human stem cell derived cardiomyocytes. The major determinants of human whole-heart function were experimentally modeled by integrating...
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| Veröffentlicht in: | Biomaterials 2015-08, Vol.60, p.20-30 |
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| creator | Stancescu, Maria Molnar, Peter McAleer, Christopher W McLamb, William Long, Christopher J Oleaga, Carlota Prot, Jean-Matthieu Hickman, James J |
| description | Abstract This article details the construction and testing of a phenotypic assay system that models in vivo cardiac function in a parallel in vitro environment with human stem cell derived cardiomyocytes. The major determinants of human whole-heart function were experimentally modeled by integrating separate 2D cellular systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model features a serum-free defined medium to enable both acute and chronic evaluation of drugs and toxins. The integration of data from both systems produced biologically relevant predictions of cardiac function in response to varying concentrations of selected drugs. Sotalol, norepinephrine and verapamil were shown to affect the measured parameters according to their specific mechanism of action, in agreement with clinical data. This system is applicable for cardiac side effect assessment, general toxicology, efficacy studies, and evaluation of in vitro cellular disease models in body-on-a-chip systems. |
| doi_str_mv | 10.1016/j.biomaterials.2015.04.035 |
| format | Article |
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The major determinants of human whole-heart function were experimentally modeled by integrating separate 2D cellular systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model features a serum-free defined medium to enable both acute and chronic evaluation of drugs and toxins. The integration of data from both systems produced biologically relevant predictions of cardiac function in response to varying concentrations of selected drugs. Sotalol, norepinephrine and verapamil were shown to affect the measured parameters according to their specific mechanism of action, in agreement with clinical data. This system is applicable for cardiac side effect assessment, general toxicology, efficacy studies, and evaluation of in vitro cellular disease models in body-on-a-chip systems.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2015.04.035</identifier><identifier>PMID: 25978005</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Advanced Basic Science ; Biomedical materials ; Cardiomyocyte ; Cell Culture Techniques - instrumentation ; Cells, Cultured ; Cellular ; Conduction ; Dentistry ; Determinants ; Drug Evaluation, Preclinical - instrumentation ; Drugs ; Equipment Design ; Force generation ; Functional assay ; Heart - drug effects ; Heart - physiology ; Human ; Humans ; In vitro testing ; Mathematical models ; Micro-Electrical-Mechanical Systems - instrumentation ; Microelectrodes ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - drug effects ; Serum-free ; Surgical implants</subject><ispartof>Biomaterials, 2015-08, Vol.60, p.20-30</ispartof><rights>Elsevier Ltd</rights><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><rights>2015 Published by Elsevier Ltd. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c604t-40aa24185bc4cf06ef57742e3387b71a3477b20ce0344f3d4a4b72a9b9b5e1143</citedby><cites>FETCH-LOGICAL-c604t-40aa24185bc4cf06ef57742e3387b71a3477b20ce0344f3d4a4b72a9b9b5e1143</cites><orcidid>0000-0001-9715-9197</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biomaterials.2015.04.035$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25978005$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stancescu, Maria</creatorcontrib><creatorcontrib>Molnar, Peter</creatorcontrib><creatorcontrib>McAleer, Christopher W</creatorcontrib><creatorcontrib>McLamb, William</creatorcontrib><creatorcontrib>Long, Christopher J</creatorcontrib><creatorcontrib>Oleaga, Carlota</creatorcontrib><creatorcontrib>Prot, Jean-Matthieu</creatorcontrib><creatorcontrib>Hickman, James J</creatorcontrib><title>A phenotypic in vitro model for the main determinants of human whole heart function</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract This article details the construction and testing of a phenotypic assay system that models in vivo cardiac function in a parallel in vitro environment with human stem cell derived cardiomyocytes. The major determinants of human whole-heart function were experimentally modeled by integrating separate 2D cellular systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model features a serum-free defined medium to enable both acute and chronic evaluation of drugs and toxins. The integration of data from both systems produced biologically relevant predictions of cardiac function in response to varying concentrations of selected drugs. Sotalol, norepinephrine and verapamil were shown to affect the measured parameters according to their specific mechanism of action, in agreement with clinical data. This system is applicable for cardiac side effect assessment, general toxicology, efficacy studies, and evaluation of in vitro cellular disease models in body-on-a-chip systems.</description><subject>Advanced Basic Science</subject><subject>Biomedical materials</subject><subject>Cardiomyocyte</subject><subject>Cell Culture Techniques - instrumentation</subject><subject>Cells, Cultured</subject><subject>Cellular</subject><subject>Conduction</subject><subject>Dentistry</subject><subject>Determinants</subject><subject>Drug Evaluation, Preclinical - instrumentation</subject><subject>Drugs</subject><subject>Equipment Design</subject><subject>Force generation</subject><subject>Functional assay</subject><subject>Heart - drug effects</subject><subject>Heart - physiology</subject><subject>Human</subject><subject>Humans</subject><subject>In vitro testing</subject><subject>Mathematical models</subject><subject>Micro-Electrical-Mechanical Systems - instrumentation</subject><subject>Microelectrodes</subject><subject>Myocytes, Cardiac - cytology</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Serum-free</subject><subject>Surgical implants</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUk1v1DAQjRCILoW_gCxOXDaMv9YJh0pVoYBUiQPlbDnOhHhJ7MV2ttp_w2_hlzXRlqpw6mlkzXtv3vhNUbyhUFKgm3fbsnFhNBmjM0MqGVBZgiiByyfFilaqWssa5NNiBVSwdb2h7KR4kdIW5jcI9rw4YbJWFYBcFdfnZNejD_mwc5Y4_-f33uUYyBhaHEgXIsk9ktE4T1qcJ47OG58TCR3pp9F4ctOHAUmPJmbSTd5mF_zL4lk3O8NXd_W0-H758fri8_rq66cvF-dXa7sBkdcCjGGCVrKxwnawwU4qJRhyXqlGUcOFUg0Di8CF6HgrjGgUM3VTNxIpFfy0ODvq7qZmxNaiz9EMehfdaOJBB-P0vx3vev0j7LUQsqKingXe3gnE8GvClPXoksVhMB7DlDRVCvhscVM9AsplzYDxxdb7I9TGkFLE7t4RBb0kqLf6YYJ6SVCD0HOCM_n1w53uqX8jmwEfjgCcf3bvMOpkHXqLrYtos26De9ycs_9k7OC8s2b4iQdM2zBFv3CoTkyD_rbc0nJKVALwGhS_BdRnykE</recordid><startdate>20150801</startdate><enddate>20150801</enddate><creator>Stancescu, Maria</creator><creator>Molnar, Peter</creator><creator>McAleer, Christopher W</creator><creator>McLamb, William</creator><creator>Long, Christopher J</creator><creator>Oleaga, Carlota</creator><creator>Prot, Jean-Matthieu</creator><creator>Hickman, James J</creator><general>Elsevier Ltd</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9715-9197</orcidid></search><sort><creationdate>20150801</creationdate><title>A phenotypic in vitro model for the main determinants of human whole heart function</title><author>Stancescu, Maria ; Molnar, Peter ; McAleer, Christopher W ; McLamb, William ; Long, Christopher J ; Oleaga, Carlota ; Prot, Jean-Matthieu ; Hickman, James J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c604t-40aa24185bc4cf06ef57742e3387b71a3477b20ce0344f3d4a4b72a9b9b5e1143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Advanced Basic Science</topic><topic>Biomedical materials</topic><topic>Cardiomyocyte</topic><topic>Cell Culture Techniques - instrumentation</topic><topic>Cells, Cultured</topic><topic>Cellular</topic><topic>Conduction</topic><topic>Dentistry</topic><topic>Determinants</topic><topic>Drug Evaluation, Preclinical - instrumentation</topic><topic>Drugs</topic><topic>Equipment Design</topic><topic>Force generation</topic><topic>Functional assay</topic><topic>Heart - drug effects</topic><topic>Heart - physiology</topic><topic>Human</topic><topic>Humans</topic><topic>In vitro testing</topic><topic>Mathematical models</topic><topic>Micro-Electrical-Mechanical Systems - instrumentation</topic><topic>Microelectrodes</topic><topic>Myocytes, Cardiac - cytology</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Serum-free</topic><topic>Surgical implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stancescu, Maria</creatorcontrib><creatorcontrib>Molnar, Peter</creatorcontrib><creatorcontrib>McAleer, Christopher W</creatorcontrib><creatorcontrib>McLamb, William</creatorcontrib><creatorcontrib>Long, Christopher J</creatorcontrib><creatorcontrib>Oleaga, Carlota</creatorcontrib><creatorcontrib>Prot, Jean-Matthieu</creatorcontrib><creatorcontrib>Hickman, James J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stancescu, Maria</au><au>Molnar, Peter</au><au>McAleer, Christopher W</au><au>McLamb, William</au><au>Long, Christopher J</au><au>Oleaga, Carlota</au><au>Prot, Jean-Matthieu</au><au>Hickman, James J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A phenotypic in vitro model for the main determinants of human whole heart function</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2015-08-01</date><risdate>2015</risdate><volume>60</volume><spage>20</spage><epage>30</epage><pages>20-30</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract This article details the construction and testing of a phenotypic assay system that models in vivo cardiac function in a parallel in vitro environment with human stem cell derived cardiomyocytes. The major determinants of human whole-heart function were experimentally modeled by integrating separate 2D cellular systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model features a serum-free defined medium to enable both acute and chronic evaluation of drugs and toxins. The integration of data from both systems produced biologically relevant predictions of cardiac function in response to varying concentrations of selected drugs. Sotalol, norepinephrine and verapamil were shown to affect the measured parameters according to their specific mechanism of action, in agreement with clinical data. 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| subjects | Advanced Basic Science Biomedical materials Cardiomyocyte Cell Culture Techniques - instrumentation Cells, Cultured Cellular Conduction Dentistry Determinants Drug Evaluation, Preclinical - instrumentation Drugs Equipment Design Force generation Functional assay Heart - drug effects Heart - physiology Human Humans In vitro testing Mathematical models Micro-Electrical-Mechanical Systems - instrumentation Microelectrodes Myocytes, Cardiac - cytology Myocytes, Cardiac - drug effects Serum-free Surgical implants |
| title | A phenotypic in vitro model for the main determinants of human whole heart function |
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