Estrategias de Ingeniería Genética para el mejoramiento de terapias avanzadas basadas en Células Estromales Mesenquimales de gelatina de Wharton de cordón umbilical (CEM-GW) y sus derivados, con potencial de uso clínico
Thesis
In the last decade, advances in understanding the role of mesenchymal stromal cells (MSCs) in homeostasis, repair and tissue regeneration, as well as regulation of inflammatory responses at local and systemic levels, have inspired prodigious efforts into the development of MSC biotechnological platforms for potential application as therapeutic tools in clinical settings. As a result, more than 1300 clinical trials worldwide have been carried out to define the therapeutic efficacy of medicinal products based on MSC cell therapy. Disappointingly, although MSCs have been shown to be safe, effectiveness studies have given inconsistent results in different clinical settings, mainly due to variable performance of the cell product during its clinical application. Therefore, strategies are still needed to improve the potency and performance of MSC-based medicinal products. One approach could include the use of gene transfer tools to increase the viability and therapeutic effect of the cells in vivo, without generating additional risks for the treated patient and there is increasing interest in the use of this strategy to generate advanced cell therapy products. However, its application in the improvement of MSC-based products has not been considerably explored. In this study, different experimental methodologies were examined to determine the feasibility and usefulness of genetically modifying MSCs and their extracellular vesicles (EVs) as a potential biotechnological tool for the development and improvement of medicinal products derived from these components. With this perspective, we present results confirming that genetic modification of MSCs using non-viral and viral methods is technically feasible and safe supporting existing initiatives towards the development of advanced methodologies for the generation of therapeutic products with a high potential for clinical application. In addition, we develop and validate technologies for the isolation and characterization of MSC-derived EVs extending the field of knowledge about this type of nanoparticle and supporting future applications of MSC-EVs in the medical context.
