Towards a Chronic Obstructive Pulmonary Disease (COPD) 3D in vitro model: Optimization of stromal and epithelial compartments of a Lung-on-Chip Platform

Chronic obstructive pulmonary disease (COPD) is a respiratory airway condition that generates chronic inflammation and airflow limitation in the lungs. It is caused mainly by chronic exposure to harmful particles or smoke (like that of cigarettes) and genetic susceptibility. Several mechanisms like inflammation, oxidative stress and an imbalance between proteases and antiproteases cause a cascade of events that lead to airway remodeling, among other pathological changes. Currently there is no cure for COPD, however, several therapies aim at ameliorating symptoms and slowing disease progression. Recently new tools to evaluate new therapeutical approaches have been developed including 2D in vitro studies, organs-on-chip (OOC) and animal models. However, 2D and animal models are not the best at mimicking human physiology. Additionally, OOCs are focused on the alveolar area of the lung, and most do not incorporate mechanisms to mimic the tidal respiration of the lungs. To account for this gap, this work aims to optimize a lung-on-chip model that accurately represents human small airways and incorporates relevant cell populations, tidal respiration and an air liquid interface(ALI). To do so, an OOC previously designed by BiomimX Srl. was implemented, and the culture conditions were optimized both in static and dynamic conditions. Platforms were analyzed through bright-field microscopy and immunofluorescence to determine cell viability, proliferation and phenotypic markers able to characterize the microtissues. In the case of the stromal compartment, Bronchial Smooth Muscle Cells (BSMCs) showed the most promise in high density monocultures cultured in SmGm-2 or Mixed media. On the other hand, for the epithelial compartment Normal Human Bronchial Epithelial (NHBEs) cells were successfully cultured with an optimized smart seeding technique in BEGM/PneumaCult ALI media. In conclusion, in this study substantial advances were made towards the development of a COPD LOC model, opening the door for new integral therapeutical strategies to be discovered and tested.

• Autores: Fragozo Mesa, Valeria
• Tipo de recurso: Trabajo de grado de pregrado
• Fecha de publicación: 2025
• Institución: Universidad de los Andes
• Repositorio: Séneca: repositorio Uniandes
• Idioma: eng
• OAI Identifier: oai:repositorio.uniandes.edu.co:1992/75471
• Acceso en línea: https://hdl.handle.net/1992/75471
• Palabra clave: Air-Liquid Interface; Chronic Obstructive Pulmonary Disease; Lung-on-Chip; in vitro Breathing; Organs-on-Chip; Small Airway; Ingeniería
• Rights: embargoedAccess
• License: Attribution-NonCommercial-NoDerivatives 4.0 International