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

dc.contributor
Universitat de Barcelona. Facultat de Medicina i Ciències de la Salut
dc.contributor.author
Falcones Olarte, Kevin Bryan
dc.date.accessioned
2022-06-21T10:17:12Z
dc.date.available
2022-06-21T10:17:12Z
dc.date.issued
2022-04-22
dc.identifier.uri
http://hdl.handle.net/10803/674606
dc.description
Programa de Doctorat en Biomedicina
en_US
dc.description.abstract
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.
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dc.format.extent
180 p.
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application/pdf
dc.language.iso
eng
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dc.publisher
Universitat de Barcelona
dc.rights.license
ADVERTIMENT. Tots els drets reservats. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.
dc.source
TDX (Tesis Doctorals en Xarxa)
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Fisiologia humana
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dc.subject
Fisiología humana
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Human physiology
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dc.subject
Malalties dels pulmons
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Enfermedades pulmonares
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Pulmonary diseases
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Cultiu de teixits
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Cultivo de tejidos
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dc.subject
Tissue culture
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Matriu extracel·lular
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Matriz extracelular
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dc.subject
Extracellular matrix
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dc.subject.other
Ciències de la Salut
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dc.title
Application of physiomimetic stimuli for realistically reproducing pathological hypoxic and micromechanical cell environments
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dc.type
info:eu-repo/semantics/doctoralThesis
dc.type
info:eu-repo/semantics/publishedVersion
dc.subject.udc
612
en_US
dc.contributor.director
Almendros López, Isaac
dc.contributor.tutor
Almendros López, Isaac
dc.embargo.terms
cap
en_US
dc.rights.accessLevel
info:eu-repo/semantics/openAccess


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