Publicação
Bioengineering of unitary tumor-stroma lung organoids in tissue-specific matrices
| Resumo: | Lung cancer, particularly non-small cell lung cancer (NSCLC), is a complex disease in terms of diagnosis and treatment. Challenges such as resistance to therapies and the inability to replicate the tumor microenvironment (TME) at the preclinical level require new strategies to accelerate the discovery and validation of new therapies. In this context, new in vitro models, namely lung cancer organoids (LCOs) formed with patient-derived cells, are emerging as promising tools for developing and testing therapies. This dissertation focused on the development of a method to obtain LCOs individually and containing different components of the TME. The organoids developed contain tumor and stromal cells, namely lung cancer-associated fibroblasts (CAFs), allowing the simulation of tumor-stroma interactions, a key factor in tumor progression and therapeutic resistance. During the bioengineering of this model, several biomaterials were also tested as cell support matrices, with the aim of mimicking the presence of the tumor extracellular matrix. Bioimaging analyses demonstrate that human collagen matrices generated organoids with defined morphologies, proliferative capacity, and secretion of key bioactive molecules in the TME. Additionally, the inclusion of decellularized porcine lung tissue matrix was explored for the fabrication of organoids specific to this tissue. In the future, the integration of these systems into chips and bioprinted structures may further increase their physiological relevance and applicability as platforms for testing therapies. |
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| Autores principais: | Cardoso, Beatriz Amador Lopes |
| Assunto: | Lung cancer Organoids Bioengineering Tumor microenvironment Biomaterials |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Aveiro |
| Idioma: | inglês |
| Origem: | RIA - Repositório Institucional da Universidade de Aveiro |
| Resumo: | Lung cancer, particularly non-small cell lung cancer (NSCLC), is a complex disease in terms of diagnosis and treatment. Challenges such as resistance to therapies and the inability to replicate the tumor microenvironment (TME) at the preclinical level require new strategies to accelerate the discovery and validation of new therapies. In this context, new in vitro models, namely lung cancer organoids (LCOs) formed with patient-derived cells, are emerging as promising tools for developing and testing therapies. This dissertation focused on the development of a method to obtain LCOs individually and containing different components of the TME. The organoids developed contain tumor and stromal cells, namely lung cancer-associated fibroblasts (CAFs), allowing the simulation of tumor-stroma interactions, a key factor in tumor progression and therapeutic resistance. During the bioengineering of this model, several biomaterials were also tested as cell support matrices, with the aim of mimicking the presence of the tumor extracellular matrix. Bioimaging analyses demonstrate that human collagen matrices generated organoids with defined morphologies, proliferative capacity, and secretion of key bioactive molecules in the TME. Additionally, the inclusion of decellularized porcine lung tissue matrix was explored for the fabrication of organoids specific to this tissue. In the future, the integration of these systems into chips and bioprinted structures may further increase their physiological relevance and applicability as platforms for testing therapies. |
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