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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

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dc.contributor.advisorSalguero López, Gustavo Andrés
dc.contributor.advisorAcosta Ampudia, Yeny Yasbleidy
dc.creatorBuitrago Gutiérrez, July Constanza
dc.creator.degreeDoctor en Ciencias Biomédicas y Biológicas
dc.creator.degreeLevelDoctorado
dc.creator.degreetypeFull time
dc.date.accessioned2024-10-10T19:13:59Z
dc.date.available2024-10-10T19:13:59Z
dc.date.created2023-07-18
dc.descriptionEn la última década, los avances en la comprensión del rol de las células estromales mesenquimales (CEM) en los diversos procesos de homeostasis, reparación y regeneración tisular, así como su papel determinante en la regulación de respuestas inflamatorias a nivel local y sistémico, han acelerado el intenso desarrollo de plataformas biotecnológicas entorno a su potencial de aplicación como herramientas terapéuticas para uso clínico. Más de 1300 ensayos clínicos a nivel global se han llevado a cabo en la última década con el objetivo de determinar la eficacia terapéutica de productos medicinales basados en terapia celular con CEM. Si bien las CEM han demostrado ser seguras, los datos clínicos conseguidos señalan resultados no consistentes en términos de efectividad en distintos escenarios clínicos, principalmente debido al desempeño del producto celular durante su aplicación clínica. Estrategias para mejorar la potencia y desempeño de productos medicinales basados en CEM podrían involucrar el uso de herramientas de transferencia génica que permitan incrementar la viabilidad y el efecto terapéutico del principio activo celular in vivo, sin generar riesgos adicionales para el paciente tratado. Aunque existe un auge actual en el uso de este tipo de estrategias para generar productos de terapia celular avanzados, su aplicación en el mejoramiento de productos basados en CEM no ha sido significativamente explorado. En este trabajo de tesis se exploraron diversas metodologías experimentales orientadas a determinar la factibilidad y utilidad de la modificación genética de las CEM y las vesículas extracelulares (VEs) derivadas de estas, como potencial herramienta biotecnológica para el desarrollo y mejoramiento de productos medicinales derivados de estos componentes para futuro uso clínico. Con esta perspectiva, el trabajo permitió confirmar que la modificación génica de este tipo celular a partir de métodos no-virales y virales, es técnicamente factible y seguro y abre una ventana de oportunidad para el desarrollo de metodologías avanzadas para la generación de productos medicinales de terapia avanzada con alto potencial de aplicación clínica. Así mismo, el trabajo introduce y valida tecnologías para el aislamiento y caracterización de VEs derivadas de CEM que amplían el campo del conocimiento sobre este tipo de nanopartículas para su futura aplicación en el contexto médico.
dc.description.abstractIn 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.
dc.format.extent180 pp
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.4872410336_43654
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/43654
dc.language.isospa
dc.publisherUniversidad del Rosario
dc.publisher.departmentEscuela de Medicina y Ciencias de la Salud
dc.publisher.programDoctorado en Ciencias Biomédicas y Biológicas
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)
dc.rights.licenciaPARGRAFO: En caso de presentarse cualquier reclamación o acción por parte de un tercero en cuanto a los derechos de autor sobre la obra en cuestión, EL AUTOR, asumirá toda la responsabilidad, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos la universidad actúa como un tercero de buena fe.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
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dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subjectCélulas estromales mesenquimales de Gelatina de Wharton
dc.subjectVesículas extracelulares
dc.subjectNucleofección
dc.subjectLentivirus
dc.subjectModificación genética
dc.subjectDiferenciación osteogénica
dc.subjectImmunomodualción
dc.subject.keywordWharton's Jelly mesenchymal stromal cells
dc.subject.keywordExtracellular vesicles
dc.subject.keywordNucleofection
dc.subject.keywordLentivirus
dc.subject.keywordGenetic modification
dc.subject.keywordOsteogenic differentiation
dc.subject.keywordImmunomodulation
dc.titleEstrategias 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
dc.title.TranslatedTitleGenetic engineering strategies for the improvement of advanced therapies based on Mesenchymal Stromal Cells from umbilical cord Wharton's jelly (CEM-GW) and their derivatives, with potential for clinical use
dc.typedoctoralThesis
dc.type.documentTesis
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersion
dc.type.spaTesis de doctorado
local.department.reportEscuela de Medicina y Ciencias de la Salud
local.regionesBogotá
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Doctorado en Ciencias Biomédicas y Biológicas