{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:22:14Z","timestamp":1793334134886,"version":"4.5.0"},"reference-count":91,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2017,3,18]],"date-time":"2017-03-18T00:00:00Z","timestamp":1489795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,3,18]],"date-time":"2017-03-18T00:00:00Z","timestamp":1489795200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,3,18]],"date-time":"2017-03-18T00:00:00Z","timestamp":1489795200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001474","name":"Singapore-MIT Alliance for Research and Technology Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001474","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Upon cardiac pathological conditions such as ischemia, microenvironmental changes instruct a series of cellular responses that trigger cardiac fibroblasts-mediated tissue adaptation and inflammation. A comprehensive model of how early environmental changes may induce cardiac fibroblasts (CF) pathological responses is far from being elucidated, partly due to the lack of approaches involving complex and simultaneous environmental stimulation. Here, we provide a first analysis of human primary CF behavior by means of a multi-stimulus microdevice for combined application of cyclic mechanical strain and controlled oxygen tension. Our findings elucidate differential human CFs responses to different combinations of the above stimuli. Individual stimuli cause proliferative effects (PHH3\n                    <jats:sup>+<\/jats:sup>\n                    mitotic cells, YAP translocation, PDGF secretion) or increase collagen presence. Interestingly, only the combination of hypoxia and a simulated loss of contractility (2% strain) is able to additionally induce increased CF release of inflammatory and pro-fibrotic cytokines and matrix metalloproteinases.\n                  <\/jats:p>","DOI":"10.7554\/elife.22847","type":"journal-article","created":{"date-parts":[[2017,3,18]],"date-time":"2017-03-18T09:00:57Z","timestamp":1489827657000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.22847","source":"Crossref","is-referenced-by-count":48,"title":["Human cardiac fibroblasts adaptive responses to controlled combined mechanical strain and oxygen changes in vitro"],"prefix":"10.7554","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4775-6676","authenticated-orcid":true,"given":"Giovanni Stefano","family":"Ugolini","sequence":"first","affiliation":[{"name":"Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2777-1043","authenticated-orcid":true,"given":"Andrea","family":"Pavesi","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore"},{"name":"Biosym IRG, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Rasponi","sequence":"additional","affiliation":[{"name":"Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco Beniamino","family":"Fiore","sequence":"additional","affiliation":[{"name":"Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Kamm","sequence":"additional","affiliation":[{"name":"Biosym IRG, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore"},{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8607-7196","authenticated-orcid":true,"given":"Monica","family":"Soncini","sequence":"additional","affiliation":[{"name":"Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2017,3,18]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1039\/c3lc50350j","article-title":"Microfluidic heart on a chip for higher throughput pharmacological 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