Development and characterization of lung extracellular matrix-based models for respiratory research
[eng] INTRODUCTION: The human respiratory system is responsible for the oxygen and carbon dioxide exchange between the body and the external environment. It is composed of organs and tissues being the lungs the pivotal organ of the system. They facilitate the exchange of gases during respiration whi...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/215601 |
| Acceso en línea: | https://hdl.handle.net/2445/215601 http://hdl.handle.net/10803/692284 |
| Access Level: | acceso abierto |
| Palabra clave: | Malalties de l'aparell respiratori Biomecànica Respiratory diseases Biomechanics |
| Sumario: | [eng] INTRODUCTION: The human respiratory system is responsible for the oxygen and carbon dioxide exchange between the body and the external environment. It is composed of organs and tissues being the lungs the pivotal organ of the system. They facilitate the exchange of gases during respiration which is vital for sustaining cellular metabolism and body’s homeostasis. Lungs are composed of a mesh of airways. The starting point is the trachea, which bifurcates into the two main bronchi that enter the right and left lungs. These bronchi are further divided into smaller bronchi and bronchioles, that finally leads to alveoli, tiny air sacs surrounded by blood vessels. The alveoli have an enormous surface area, allowing efficient diffusion of oxygen and carbon dioxide between air and the bloodstream. The oxygen is diffused to the capillaries and bound to haemoglobin inside the red blood cells (RBC) for their transportation across the whole body. Simultaneously, the waste product from the metabolism (carbon dioxide) is released from the capillaries to the alveoli to be released during exhalation. HYPOTHESIS AND OBJECTIVES: According to the background previously explained, the hypotheses of this thesis are: a) The ECM lung-derived hydrogels will release bioactive therapeutic molecules which could interact with epithelial alveolar cells. b) Physiomimetic hydrogels derived from decellularized lungs will provide a most realistic substrate for culturing MSCs which will enhance the therapeutic effects of their secreted vesicles. c) Therapeutic intratracheal administration of lung derived hydrogel will ameliorate the pulmonary outcomes and reduce the physiologic changes in an ALI rat model. d) Aging has important implications in the ECM composition and stiffness, potentially modulating the behaviour of pulmonary cells and increasing the susceptibility to chronic lung diseases. e) The difference in ECM composition during aging will affect the ECM stiffness at different level of tissular strain. Therefore, in order to improve therapies in severe respiratory diseases, the general aim of the project is to characterize the ECM - based approaches to be used for better understanding and outcome in ARDS. SPECIFIC AIMS: a) To characterize the proteins produced during the development of L-HG and released at different times and how they impact alveolar epithelial cells immunoresponse and migration capacity. b) To characterize the secretome/EV’s of MSCs cultured in conventional flasks and on lung hydrogels and to test the therapeutic effects of both EVs released from MSCs and/or ECM-vesicles from lung-derived hydrogel in a wound-healing experimental model of lung repair. c) To assess whether ARDS therapy can be improved by using L-HG for intratracheal instillation on an in vivo LPS – induced ALI model compared to the cellular approach using MSCs. d) To investigate how aging affects the composition and stiffness of the lung ECM and how it can modulate its crosstalk between MSCs. |
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