{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T08:48:23Z","timestamp":1781340503299,"version":"3.54.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T00:00:00Z","timestamp":1607558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Department of Information and Communication Technologies of the Universitat Pompeu Fabra"},{"DOI":"10.13039\/100006099","name":"Whitaker International Fellows and Scholars Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006099","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Government","award":["RYC-2015-18888"],"award-info":[{"award-number":["RYC-2015-18888"]}]},{"name":"Spanish Government","award":["MDM-2015-0502"],"award-info":[{"award-number":["MDM-2015-0502"]}]},{"name":"Spanish Government","award":["HOLOA-DPI2016-80283-C2-1-R"],"award-info":[{"award-number":["HOLOA-DPI2016-80283-C2-1-R"]}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["Disc4All-MSCA-2020-ITN-ETN 955735"],"award-info":[{"award-number":["Disc4All-MSCA-2020-ITN-ETN 955735"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Low back pain is responsible for more global disability than any other condition. Its incidence is closely related to intervertebral disc (IVD) failure, which is likely caused by an accumulation of microtrauma within the IVD. Crucial factors in microtrauma development are not entirely known yet, probably because their exploration in vivo or in vitro remains tremendously challenging. In silico modelling is, therefore, definitively appealing, and shall include approaches to integrate influences of multiple cell stimuli at the microscale. Accordingly, this study introduces a hybrid Agent-based (AB) model in IVD research and exploits network modelling solutions in systems biology to mimic the cellular behaviour of Nucleus Pulposus cells exposed to a 3D multifactorial biochemical environment, based on mathematical integrations of existing experimental knowledge. Cellular activity reflected by mRNA expression of Aggrecan, Collagen type I, Collagen type II, MMP-3 and ADAMTS were calculated for inflamed and non-inflamed cells. mRNA expression over long periods of time is additionally determined including cell viability estimations. Model predictions were eventually validated with independent experimental data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>As it combines experimental data to simulate cell behaviour exposed to a multifactorial environment, the present methodology was able to reproduce cell death within 3\u2009days under glucose deprivation and a 50% decrease in cell viability after 7\u2009days in an acidic environment. Cellular mRNA expression under non-inflamed conditions simulated a quantifiable catabolic shift under an adverse cell environment, and model predictions of mRNA expression of inflamed cells provide new explanation possibilities for unexpected results achieved in experimental research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availabilityand implementation<\/jats:title>\n                    <jats:p>The AB model as well as used mathematical functions were built with open source software. Final functions implemented in the AB model and complete AB model parameters are provided as Supplementary Material. Experimental input and validation data were provided through referenced, published papers. The code corresponding to the model can be shared upon request and shall be reused after proper training.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa939","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T08:49:08Z","timestamp":1603788548000},"page":"1246-1253","source":"Crossref","is-referenced-by-count":19,"title":["Simulating intervertebral disc cell behaviour within 3D multifactorial environments"],"prefix":"10.1093","volume":"37","author":[{"given":"L","family":"Baumgartner","sequence":"first","affiliation":[{"name":"BCN MedTech, Department of Information and Communication Technologies, Universitat Pompeu Fabra , 08018 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J J","family":"Reagh","sequence":"additional","affiliation":[{"name":"BCN MedTech, Department of Information and Communication Technologies, Universitat Pompeu Fabra , 08018 Barcelona, Spain"},{"name":"University of Cincinnati College of Medicine , Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Gonz\u00e1lez Ballester","sequence":"additional","affiliation":[{"name":"BCN MedTech, Department of Information and Communication Technologies, Universitat Pompeu Fabra , 08018 Barcelona, Spain"},{"name":"ICREA , Pg. Lluis Companys 23, 08010 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Noailly","sequence":"additional","affiliation":[{"name":"BCN MedTech, Department of Information and Communication Technologies, Universitat Pompeu Fabra , 08018 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,10]]},"reference":[{"key":"2023051706060256800_btaa939-B1","first-page":"484","author":"Baumgartner","year":"2019"},{"key":"2023051706060256800_btaa939-B2","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s00586-003-0616-x","article-title":"Effect of nutrient deprivation on the viability of intervertebral disc cells","volume":"13","author":"Bibby","year":"2004","journal-title":"Eur. 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