Application of physiomimetic stimuli for realistically reproducing pathological hypoxic and micromechanical cell environments

[eng] HYPOTHESIS 1: The frequency and the plateau values displayed by OSA-related IH patterns are important to understand the endothelial dysfunction triggered by OSA. AIM 1: A) General: To evaluate the contribution of frequency and magnitude of IH in an in vitro model of aortic wound closure. B) Sp...

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Autor: Falcones Olarte, Kevin Bryan
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/186847
Acceso en línea:https://hdl.handle.net/2445/186847
http://hdl.handle.net/10803/674606
Access Level:acceso abierto
Palabra clave:Fisiologia humana
Malalties del pulmó
Cultiu de teixits
Matriu extracel·lular
Human physiology
Pulmonary diseases
Tissue culture
Extracellular matrix
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oai_identifier_str oai:diposit.ub.edu:2445/186847
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Application of physiomimetic stimuli for realistically reproducing pathological hypoxic and micromechanical cell environments
title Application of physiomimetic stimuli for realistically reproducing pathological hypoxic and micromechanical cell environments
spellingShingle Application of physiomimetic stimuli for realistically reproducing pathological hypoxic and micromechanical cell environments
Falcones Olarte, Kevin Bryan
Fisiologia humana
Malalties del pulmó
Cultiu de teixits
Matriu extracel·lular
Human physiology
Pulmonary diseases
Tissue culture
Extracellular matrix
title_short Application of physiomimetic stimuli for realistically reproducing pathological hypoxic and micromechanical cell environments
title_full Application of physiomimetic stimuli for realistically reproducing pathological hypoxic and micromechanical cell environments
title_fullStr Application of physiomimetic stimuli for realistically reproducing pathological hypoxic and micromechanical cell environments
title_full_unstemmed Application of physiomimetic stimuli for realistically reproducing pathological hypoxic and micromechanical cell environments
title_sort Application of physiomimetic stimuli for realistically reproducing pathological hypoxic and micromechanical cell environments
dc.creator.none.fl_str_mv Falcones Olarte, Kevin Bryan
author Falcones Olarte, Kevin Bryan
author_facet Falcones Olarte, Kevin Bryan
author_role author
dc.contributor.none.fl_str_mv Almendros López, Isaac
Universitat de Barcelona. Facultat de Medicina i Ciències de la Salut
dc.subject.none.fl_str_mv Fisiologia humana
Malalties del pulmó
Cultiu de teixits
Matriu extracel·lular
Human physiology
Pulmonary diseases
Tissue culture
Extracellular matrix
topic Fisiologia humana
Malalties del pulmó
Cultiu de teixits
Matriu extracel·lular
Human physiology
Pulmonary diseases
Tissue culture
Extracellular matrix
description [eng] HYPOTHESIS 1: The frequency and the plateau values displayed by OSA-related IH patterns are important to understand the endothelial dysfunction triggered by OSA. AIM 1: A) General: To evaluate the contribution of frequency and magnitude of IH in an in vitro model of aortic wound closure. B) Specific: 1) To build up an in vitro device that enable the modulation of frequency and magnitude of IH. 2) To quantify the wound closure index of a human aortic endothelial monolayer cultured under relevant constant hypoxic and normoxic values. 3) To compare and contrast the effect on the wound closure index of different cycling rates and plateau values of IH cycles and the contribution of the maximum and minimum values. HYPOTHESIS 2: The oxygen gradients observed in the tumor microenvironment could affect the cross-talk between macrophages and tumor cells leading to macrophage recruitment and cancer malignancy by creating an immune-permissive tumor microenvironment. AIM 2: a) General: To study the potential role of the O2 gradient, found in solid tumors, on macrophage recruitment and phenotype and the importance in cancer development. b) Specific: 1) To design and construct a co-culture in vitro model that enable simultaneously culture of two types of cells under a different oxygenation paradigm. 2) To quantify macrophage recruitment and evaluate the polarization of macrophages to M1/M2 phenotypes when co-cultured with tumor cells exposed to differential levels of oxygen. 3) To evaluate the cell growth of cancer cells and quantify the expression of relevant genes related to the macrophages roles in the tumor microenvironment. HYPOTHESIS 3: The biophysical preconditioning of LMSC with physiological lung ECM cues could improve their therapeutic potential for the treatment of ARDS. AIM 3: A) General: To study the effects of biophysically fostered LMSC in a rat ventilator-induced lung injury (VILI) model of ARDS. B) Specific: 1) To build up an in vitro model to culture LMSC on a lung decellularised scaffold and subjected to cyclic stretch. 2) To evaluate the effect of Preconditioned LMSC on respiratory mechanics and pulmonary edema of rats subjected to VILI. 3) To assess the effect of Preconditioned LMSC on lung injury markers and immune cells from the BAL. 4) To study the capacity of Preconditioned LMSC to engraft to the ARDS rat lung after transplantation. Hypothesis 4 Culturing LMSC in 3D within lung ECM-derived hydrogels could provide a more similar biophysical milieu to the native tissue which could improve their therapeutic potential affecting relevant mechanobiology outcomes. Aim 4 General To develop a 3D hydrogel model based on lung ECM cues to study therapeutic relevant outcomes on LMSC with the ultimate purpose of developing improved therapeutic approaches for lung inflammatory diseases. Specific 1) To develop and characterize a material derived from the lung pig ECM to culture LMSC in 3D. 2) To evaluate macroscopically the interaction between the hydrogel and the LMSC. 3) To study cell adhesion and quantify CXCR4 gene expression of LMSC cultured in this 3D model. 4) To evaluate inflammatory markers of LMSC, previously cultured in lung hydrogels, in a co- culture epithelial model of LPS-induced acute lung injury.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/186847
http://hdl.handle.net/10803/674606
url https://hdl.handle.net/2445/186847
http://hdl.handle.net/10803/674606
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv (c) Falcones Olarte, Kevin Bryan, 2022
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Falcones Olarte, Kevin Bryan, 2022
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Facultat - Medicina i Ciències de la Salut
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869425283039232000
spelling Application of physiomimetic stimuli for realistically reproducing pathological hypoxic and micromechanical cell environmentsFalcones Olarte, Kevin BryanFisiologia humanaMalalties del pulmóCultiu de teixitsMatriu extracel·lularHuman physiologyPulmonary diseasesTissue cultureExtracellular matrix[eng] HYPOTHESIS 1: The frequency and the plateau values displayed by OSA-related IH patterns are important to understand the endothelial dysfunction triggered by OSA. AIM 1: A) General: To evaluate the contribution of frequency and magnitude of IH in an in vitro model of aortic wound closure. B) Specific: 1) To build up an in vitro device that enable the modulation of frequency and magnitude of IH. 2) To quantify the wound closure index of a human aortic endothelial monolayer cultured under relevant constant hypoxic and normoxic values. 3) To compare and contrast the effect on the wound closure index of different cycling rates and plateau values of IH cycles and the contribution of the maximum and minimum values. HYPOTHESIS 2: The oxygen gradients observed in the tumor microenvironment could affect the cross-talk between macrophages and tumor cells leading to macrophage recruitment and cancer malignancy by creating an immune-permissive tumor microenvironment. AIM 2: a) General: To study the potential role of the O2 gradient, found in solid tumors, on macrophage recruitment and phenotype and the importance in cancer development. b) Specific: 1) To design and construct a co-culture in vitro model that enable simultaneously culture of two types of cells under a different oxygenation paradigm. 2) To quantify macrophage recruitment and evaluate the polarization of macrophages to M1/M2 phenotypes when co-cultured with tumor cells exposed to differential levels of oxygen. 3) To evaluate the cell growth of cancer cells and quantify the expression of relevant genes related to the macrophages roles in the tumor microenvironment. HYPOTHESIS 3: The biophysical preconditioning of LMSC with physiological lung ECM cues could improve their therapeutic potential for the treatment of ARDS. AIM 3: A) General: To study the effects of biophysically fostered LMSC in a rat ventilator-induced lung injury (VILI) model of ARDS. B) Specific: 1) To build up an in vitro model to culture LMSC on a lung decellularised scaffold and subjected to cyclic stretch. 2) To evaluate the effect of Preconditioned LMSC on respiratory mechanics and pulmonary edema of rats subjected to VILI. 3) To assess the effect of Preconditioned LMSC on lung injury markers and immune cells from the BAL. 4) To study the capacity of Preconditioned LMSC to engraft to the ARDS rat lung after transplantation. Hypothesis 4 Culturing LMSC in 3D within lung ECM-derived hydrogels could provide a more similar biophysical milieu to the native tissue which could improve their therapeutic potential affecting relevant mechanobiology outcomes. Aim 4 General To develop a 3D hydrogel model based on lung ECM cues to study therapeutic relevant outcomes on LMSC with the ultimate purpose of developing improved therapeutic approaches for lung inflammatory diseases. Specific 1) To develop and characterize a material derived from the lung pig ECM to culture LMSC in 3D. 2) To evaluate macroscopically the interaction between the hydrogel and the LMSC. 3) To study cell adhesion and quantify CXCR4 gene expression of LMSC cultured in this 3D model. 4) To evaluate inflammatory markers of LMSC, previously cultured in lung hydrogels, in a co- culture epithelial model of LPS-induced acute lung injury.Universitat de BarcelonaAlmendros López, IsaacUniversitat de Barcelona. Facultat de Medicina i Ciències de la Salut2022info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/186847http://hdl.handle.net/10803/674606Tesis Doctorals - Facultat - Medicina i Ciències de la Salutreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Falcones Olarte, Kevin Bryan, 2022info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1868472026-05-27T06:46:51Z
score 15,301603

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