Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug testing
While interstitial fibrosis plays a significant role in heart failure, our understanding of disease progression in humans is limited. To address this limitation, we have engineered a cardiac-fibrosis-on-a-chip model consisting of a microfabricated device with live force measurement capabilities usin...
Gespeichert in:
| Veröffentlicht in: | Biomaterials 2020-03, Vol.233, p.119741-119741, Article 119741 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 119741 |
|---|---|
| container_issue | |
| container_start_page | 119741 |
| container_title | Biomaterials |
| container_volume | 233 |
| creator | Mastikhina, Olya Moon, Byeong-Ui Williams, Kenneth Hatkar, Rupal Gustafson, Dakota Mourad, Omar Sun, Xuetao Koo, Margaret Lam, Alan Y.L. Sun, Yu Fish, Jason E. Young, Edmond W.K. Nunes, Sara S. |
| description | While interstitial fibrosis plays a significant role in heart failure, our understanding of disease progression in humans is limited. To address this limitation, we have engineered a cardiac-fibrosis-on-a-chip model consisting of a microfabricated device with live force measurement capabilities using co-cultured human cardiac fibroblasts and pluripotent stem cell-derived cardiomyocytes. Transforming growth factor-β was used as a trigger for fibrosis. Here, we have reproduced the classic hallmarks of fibrosis-induced heart failure including high collagen deposition, increased tissue stiffness, BNP secretion, and passive tension. Force of contraction was significantly decreased in fibrotic tissues that displayed a transcriptomic signature consistent with human cardiac fibrosis/heart failure. Treatment with an anti-fibrotic drug decreased tissue stiffness and BNP secretion, with corresponding changes in the transcriptomic signature. This model represents an accessible approach to study human heart failure in vitro, and allows for testing anti-fibrotic drugs while facilitating the real-time assessment of cardiomyocyte function.
[Display omitted] |
| doi_str_mv | 10.1016/j.biomaterials.2019.119741 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2337071847</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0142961219308592</els_id><sourcerecordid>2337071847</sourcerecordid><originalsourceid>FETCH-LOGICAL-c489t-bd14062130f6328b91bb33c31d750c618ebd9003b7dc451f4d223444c03a1b833</originalsourceid><addsrcrecordid>eNqNkEtPHDEQhC0UBAvJX4isnHKZxW17XtwiIICExCU5W370gDfzwp5B4t_TaEnEMRdbtqq6uj7GvoHYgoDqbLd1cRrsginaPm-lgHYL0NYaDtgGmropylaUn9hGgJZFW4E8Zic57wS9hZZH7FhBK2tZwoblm3WwI_c2hWg976JLU465mMbCFv4xznyYAvY8obdzXNaeYjMPMaPNyB9t3w82_cncjoGGjDxjekZu6YPPpO2mNHA6eEjrAyfrEseHz-ywo8Xxy_t9yn7_vPp1cVPc3V_fXvy4K7xu2qVwgdatJCjRVUo2rgXnlPIKQl0KX0GDLrRCKFcHr0vodJBSaa29UBZco9Qp-76fO6fpaaVsM8Tsse_tiNOajVSqFjU0uibp-V7qqX5O2Jk5RWr2YkCYN-hmZz5CN2_QzR46mb--56xuwPDP-pcyCS73AqS2zxGTyT7i6DFE4rqYMMX_yXkF5t-abw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2337071847</pqid></control><display><type>article</type><title>Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug testing</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Mastikhina, Olya ; Moon, Byeong-Ui ; Williams, Kenneth ; Hatkar, Rupal ; Gustafson, Dakota ; Mourad, Omar ; Sun, Xuetao ; Koo, Margaret ; Lam, Alan Y.L. ; Sun, Yu ; Fish, Jason E. ; Young, Edmond W.K. ; Nunes, Sara S.</creator><creatorcontrib>Mastikhina, Olya ; Moon, Byeong-Ui ; Williams, Kenneth ; Hatkar, Rupal ; Gustafson, Dakota ; Mourad, Omar ; Sun, Xuetao ; Koo, Margaret ; Lam, Alan Y.L. ; Sun, Yu ; Fish, Jason E. ; Young, Edmond W.K. ; Nunes, Sara S.</creatorcontrib><description>While interstitial fibrosis plays a significant role in heart failure, our understanding of disease progression in humans is limited. To address this limitation, we have engineered a cardiac-fibrosis-on-a-chip model consisting of a microfabricated device with live force measurement capabilities using co-cultured human cardiac fibroblasts and pluripotent stem cell-derived cardiomyocytes. Transforming growth factor-β was used as a trigger for fibrosis. Here, we have reproduced the classic hallmarks of fibrosis-induced heart failure including high collagen deposition, increased tissue stiffness, BNP secretion, and passive tension. Force of contraction was significantly decreased in fibrotic tissues that displayed a transcriptomic signature consistent with human cardiac fibrosis/heart failure. Treatment with an anti-fibrotic drug decreased tissue stiffness and BNP secretion, with corresponding changes in the transcriptomic signature. This model represents an accessible approach to study human heart failure in vitro, and allows for testing anti-fibrotic drugs while facilitating the real-time assessment of cardiomyocyte function.
[Display omitted]</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2019.119741</identifier><identifier>PMID: 31927251</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Cardiac fibrosis ; Carvediolol ; Cells, Cultured ; Disease modeling ; Extracellular vesicles ; Fibroblasts - pathology ; Fibrosis ; Force of contraction ; Heart failure ; Human stem cell-derived cardiomyocytes ; Humans ; Lab-On-A-Chip Devices ; Losartan ; microRNA ; Myocardium - pathology ; Myocytes, Cardiac - pathology ; Organ-on-a-chip ; Pharmaceutical Preparations ; Pirfenidone ; Tissue engineering</subject><ispartof>Biomaterials, 2020-03, Vol.233, p.119741-119741, Article 119741</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c489t-bd14062130f6328b91bb33c31d750c618ebd9003b7dc451f4d223444c03a1b833</citedby><cites>FETCH-LOGICAL-c489t-bd14062130f6328b91bb33c31d750c618ebd9003b7dc451f4d223444c03a1b833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biomaterials.2019.119741$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31927251$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mastikhina, Olya</creatorcontrib><creatorcontrib>Moon, Byeong-Ui</creatorcontrib><creatorcontrib>Williams, Kenneth</creatorcontrib><creatorcontrib>Hatkar, Rupal</creatorcontrib><creatorcontrib>Gustafson, Dakota</creatorcontrib><creatorcontrib>Mourad, Omar</creatorcontrib><creatorcontrib>Sun, Xuetao</creatorcontrib><creatorcontrib>Koo, Margaret</creatorcontrib><creatorcontrib>Lam, Alan Y.L.</creatorcontrib><creatorcontrib>Sun, Yu</creatorcontrib><creatorcontrib>Fish, Jason E.</creatorcontrib><creatorcontrib>Young, Edmond W.K.</creatorcontrib><creatorcontrib>Nunes, Sara S.</creatorcontrib><title>Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug testing</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>While interstitial fibrosis plays a significant role in heart failure, our understanding of disease progression in humans is limited. To address this limitation, we have engineered a cardiac-fibrosis-on-a-chip model consisting of a microfabricated device with live force measurement capabilities using co-cultured human cardiac fibroblasts and pluripotent stem cell-derived cardiomyocytes. Transforming growth factor-β was used as a trigger for fibrosis. Here, we have reproduced the classic hallmarks of fibrosis-induced heart failure including high collagen deposition, increased tissue stiffness, BNP secretion, and passive tension. Force of contraction was significantly decreased in fibrotic tissues that displayed a transcriptomic signature consistent with human cardiac fibrosis/heart failure. Treatment with an anti-fibrotic drug decreased tissue stiffness and BNP secretion, with corresponding changes in the transcriptomic signature. This model represents an accessible approach to study human heart failure in vitro, and allows for testing anti-fibrotic drugs while facilitating the real-time assessment of cardiomyocyte function.
[Display omitted]</description><subject>Cardiac fibrosis</subject><subject>Carvediolol</subject><subject>Cells, Cultured</subject><subject>Disease modeling</subject><subject>Extracellular vesicles</subject><subject>Fibroblasts - pathology</subject><subject>Fibrosis</subject><subject>Force of contraction</subject><subject>Heart failure</subject><subject>Human stem cell-derived cardiomyocytes</subject><subject>Humans</subject><subject>Lab-On-A-Chip Devices</subject><subject>Losartan</subject><subject>microRNA</subject><subject>Myocardium - pathology</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Organ-on-a-chip</subject><subject>Pharmaceutical Preparations</subject><subject>Pirfenidone</subject><subject>Tissue engineering</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkEtPHDEQhC0UBAvJX4isnHKZxW17XtwiIICExCU5W370gDfzwp5B4t_TaEnEMRdbtqq6uj7GvoHYgoDqbLd1cRrsginaPm-lgHYL0NYaDtgGmropylaUn9hGgJZFW4E8Zic57wS9hZZH7FhBK2tZwoblm3WwI_c2hWg976JLU465mMbCFv4xznyYAvY8obdzXNaeYjMPMaPNyB9t3w82_cncjoGGjDxjekZu6YPPpO2mNHA6eEjrAyfrEseHz-ywo8Xxy_t9yn7_vPp1cVPc3V_fXvy4K7xu2qVwgdatJCjRVUo2rgXnlPIKQl0KX0GDLrRCKFcHr0vodJBSaa29UBZco9Qp-76fO6fpaaVsM8Tsse_tiNOajVSqFjU0uibp-V7qqX5O2Jk5RWr2YkCYN-hmZz5CN2_QzR46mb--56xuwPDP-pcyCS73AqS2zxGTyT7i6DFE4rqYMMX_yXkF5t-abw</recordid><startdate>202003</startdate><enddate>202003</enddate><creator>Mastikhina, Olya</creator><creator>Moon, Byeong-Ui</creator><creator>Williams, Kenneth</creator><creator>Hatkar, Rupal</creator><creator>Gustafson, Dakota</creator><creator>Mourad, Omar</creator><creator>Sun, Xuetao</creator><creator>Koo, Margaret</creator><creator>Lam, Alan Y.L.</creator><creator>Sun, Yu</creator><creator>Fish, Jason E.</creator><creator>Young, Edmond W.K.</creator><creator>Nunes, Sara S.</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>7X8</scope></search><sort><creationdate>202003</creationdate><title>Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug testing</title><author>Mastikhina, Olya ; Moon, Byeong-Ui ; Williams, Kenneth ; Hatkar, Rupal ; Gustafson, Dakota ; Mourad, Omar ; Sun, Xuetao ; Koo, Margaret ; Lam, Alan Y.L. ; Sun, Yu ; Fish, Jason E. ; Young, Edmond W.K. ; Nunes, Sara S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c489t-bd14062130f6328b91bb33c31d750c618ebd9003b7dc451f4d223444c03a1b833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cardiac fibrosis</topic><topic>Carvediolol</topic><topic>Cells, Cultured</topic><topic>Disease modeling</topic><topic>Extracellular vesicles</topic><topic>Fibroblasts - pathology</topic><topic>Fibrosis</topic><topic>Force of contraction</topic><topic>Heart failure</topic><topic>Human stem cell-derived cardiomyocytes</topic><topic>Humans</topic><topic>Lab-On-A-Chip Devices</topic><topic>Losartan</topic><topic>microRNA</topic><topic>Myocardium - pathology</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Organ-on-a-chip</topic><topic>Pharmaceutical Preparations</topic><topic>Pirfenidone</topic><topic>Tissue engineering</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mastikhina, Olya</creatorcontrib><creatorcontrib>Moon, Byeong-Ui</creatorcontrib><creatorcontrib>Williams, Kenneth</creatorcontrib><creatorcontrib>Hatkar, Rupal</creatorcontrib><creatorcontrib>Gustafson, Dakota</creatorcontrib><creatorcontrib>Mourad, Omar</creatorcontrib><creatorcontrib>Sun, Xuetao</creatorcontrib><creatorcontrib>Koo, Margaret</creatorcontrib><creatorcontrib>Lam, Alan Y.L.</creatorcontrib><creatorcontrib>Sun, Yu</creatorcontrib><creatorcontrib>Fish, Jason E.</creatorcontrib><creatorcontrib>Young, Edmond W.K.</creatorcontrib><creatorcontrib>Nunes, Sara S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mastikhina, Olya</au><au>Moon, Byeong-Ui</au><au>Williams, Kenneth</au><au>Hatkar, Rupal</au><au>Gustafson, Dakota</au><au>Mourad, Omar</au><au>Sun, Xuetao</au><au>Koo, Margaret</au><au>Lam, Alan Y.L.</au><au>Sun, Yu</au><au>Fish, Jason E.</au><au>Young, Edmond W.K.</au><au>Nunes, Sara S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug testing</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2020-03</date><risdate>2020</risdate><volume>233</volume><spage>119741</spage><epage>119741</epage><pages>119741-119741</pages><artnum>119741</artnum><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>While interstitial fibrosis plays a significant role in heart failure, our understanding of disease progression in humans is limited. To address this limitation, we have engineered a cardiac-fibrosis-on-a-chip model consisting of a microfabricated device with live force measurement capabilities using co-cultured human cardiac fibroblasts and pluripotent stem cell-derived cardiomyocytes. Transforming growth factor-β was used as a trigger for fibrosis. Here, we have reproduced the classic hallmarks of fibrosis-induced heart failure including high collagen deposition, increased tissue stiffness, BNP secretion, and passive tension. Force of contraction was significantly decreased in fibrotic tissues that displayed a transcriptomic signature consistent with human cardiac fibrosis/heart failure. Treatment with an anti-fibrotic drug decreased tissue stiffness and BNP secretion, with corresponding changes in the transcriptomic signature. This model represents an accessible approach to study human heart failure in vitro, and allows for testing anti-fibrotic drugs while facilitating the real-time assessment of cardiomyocyte function.
[Display omitted]</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>31927251</pmid><doi>10.1016/j.biomaterials.2019.119741</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0142-9612 |
| ispartof | Biomaterials, 2020-03, Vol.233, p.119741-119741, Article 119741 |
| issn | 0142-9612 1878-5905 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2337071847 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Cardiac fibrosis Carvediolol Cells, Cultured Disease modeling Extracellular vesicles Fibroblasts - pathology Fibrosis Force of contraction Heart failure Human stem cell-derived cardiomyocytes Humans Lab-On-A-Chip Devices Losartan microRNA Myocardium - pathology Myocytes, Cardiac - pathology Organ-on-a-chip Pharmaceutical Preparations Pirfenidone Tissue engineering |
| title | Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug testing |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T16%3A09%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Human%20cardiac%20fibrosis-on-a-chip%20model%20recapitulates%20disease%20hallmarks%20and%20can%20serve%20as%20a%20platform%20for%20drug%20testing&rft.jtitle=Biomaterials&rft.au=Mastikhina,%20Olya&rft.date=2020-03&rft.volume=233&rft.spage=119741&rft.epage=119741&rft.pages=119741-119741&rft.artnum=119741&rft.issn=0142-9612&rft.eissn=1878-5905&rft_id=info:doi/10.1016/j.biomaterials.2019.119741&rft_dat=%3Cproquest_cross%3E2337071847%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2337071847&rft_id=info:pmid/31927251&rft_els_id=S0142961219308592&rfr_iscdi=true |