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dc.contributor.authorGualda Manzano, Emilio José
dc.contributor.authorMarsal, Maria
dc.contributor.authorIsidro, Inês
dc.contributor.authorAlmeida, Jaime
dc.contributor.otherUniversitat Politècnica de Catalunya. Departament d'Enginyeria Agroalimentària i Biotecnologia
dc.date.accessioned2021-03-17T12:43:59Z
dc.date.available2021-03-17T12:43:59Z
dc.date.issued2020-12
dc.identifier.citationGualda Manzano, E.J. [et al.]. A computational diffusion model to study antibody transport within reconstructed tumor microenvironments. "BMC bioinformatics", Desembre 2020, vol. 21, núm. 1.
dc.identifier.issn1471-2105
dc.identifier.urihttp://hdl.handle.net/2117/341867
dc.description.abstractAntibodies revolutionized cancer treatment over the past decades. Despite their successfully application, there are still challenges to overcome to improve efficacy, such as the heterogeneous distribution of antibodies within tumors. Tumor microenvironment features, such as the distribution of tumor and other cell types and the composition of the extracellular matrix may work together to hinder antibodies from reaching the target tumor cells. To understand these interactions, we propose a framework combining in vitro and in silico models. We took advantage of in vitro cancer models previously developed by our group, consisting of tumor cells and fibroblasts co-cultured in 3D within alginate capsules, for reconstruction of tumor microenvironment features. Results: In this work, an experimental-computational framework of antibody transport within alginate capsules was established, assuming a purely diffusive transport, combined with an exponential saturation effect that mimics the saturation of binding sites on the cell surface. Our tumor microenvironment in vitro models were challenged with a fluorescent antibody and its transport recorded using light sheet fluorescence microscopy. Diffusion and saturation parameters of the computational model were adjusted to reproduce the experimental antibody distribution, with root mean square error under 5%. This computational framework is flexible and can simulate different random distributions of tumor microenvironment elements (fibroblasts, cancer cells and collagen fibers) within the capsule. The random distribution algorithm can be tuned to follow the general patterns observed in the experimental models. Conclusions: We present a computational and microscopy framework to track and simulate antibody transport within the tumor microenvironment that complements the previously established in vitro models platform. This framework paves the way to the development of a valuable tool to study the influence of different components of the tumor microenvironment on antibody transport.
dc.description.sponsorshipThis work was funded by: Fundação para a Ciência e Tecnologia (FCT) through PhD fellowship PD/BD/114047/2015; iNOVA4Health (UIDB/04462/2020), a program fnancially supported by FCT/Portuguese Ministry for Science, Technology and Higher Education, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement; the Spanish Ministry of Economy and Competitiveness through the “Severo Ochoa” program for Centres of Excellence in R&D (SEV-2015-0522) and Ramon y Cajal program (RYC-2015-1793); Fundació Privada Cellex; Fundació Mir-Puig; Generalitat de Catalunya through the CERCA program; European Commission Horizon 2020 LASER LAB Europe (grant agreement 654148). The funding bodies did not play any role in the design of the study and collection, analysis, and interpretation of data or in writing the manuscript.
dc.language.isoeng
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Spain
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.subjectÀrees temàtiques de la UPC::Ciències de la salut::Medicina::Medicina interna
dc.subject.lcshFluorescence microscopy
dc.subject.otherAntibody difusion
dc.subject.otherTumor microenvironment
dc.subject.other3D in vitro cancer models
dc.subject.otherComputational modelling
dc.subject.otherLight sheet fuorescence microscopy
dc.titleA computational diffusion model to study antibody transport within reconstructed tumor microenvironments
dc.typeArticle
dc.subject.lemacTumors -- Models matemàtics
dc.identifier.doi10.1186/s12859-020-03854-2
dc.relation.publisherversionhttps://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-020-03854-2
dc.rights.accessOpen Access
local.identifier.drac30378993
dc.description.versionPostprint (published version)
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/H2020/654148/EU/The Integrated Initiative of European Laser Research Infrastructures/LASERLAB-EUROPE
local.citation.authorGualda Manzano, Emilio Jose; Marsal, M.; Isidro, I.; Almeida, J.
local.citation.publicationNameBMC bioinformatics
local.citation.volume21
local.citation.number1


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Attribution-NonCommercial-NoDerivs 3.0 Spain
Except where otherwise noted, content on this work is licensed under a Creative Commons license : Attribution-NonCommercial-NoDerivs 3.0 Spain