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Evaluación del efecto inmunomodulador de los cuerpos apoptóticos de células estromales mesenquimales de Gelatina de Wharton
dc.rights.license | Reconocimiento 4.0 Internacional |
dc.contributor.advisor | Salguero, Gustavo |
dc.contributor.author | Beltran Ricaurte, Karl Michael |
dc.date.accessioned | 2023-01-30T16:54:07Z |
dc.date.available | 2023-01-30T16:54:07Z |
dc.date.issued | 2022-11-18 |
dc.identifier.uri | https://repositorio.unal.edu.co/handle/unal/83183 |
dc.description | Ilustraciones, fotografías a color, |
dc.description.abstract | Las inmunoterapias basadas en células estromales mesenquimales (CEM) representan herramientas para el tratamiento de enfermedades inflamatorias. Sin embargo, su aplicación clínica actualmente es un reto. La biodistribución de las CEM parece ser deficiente, lo que promueve la activación de la apoptosis y la liberación de cuerpos apoptóticos (AB). Dado que recientemente se ha propuesto una interacción entre los AB derivados de las CEM (CEM-AB) y componentes del sistema inmunitario, en este proyecto se demostró que los CEM-AB ejercen efectos inmunomoduladores sinérgicos en modelos de inflamación in-vitro. Para lo anterior, se obtuvieron CEM de la gelatina de Wharton (WJ) mediante un proceso de disgregación. La exposición a la irradiación gama (25Gy) indujo eficazmente la apoptosis; tal y como demostraron la fragmentación del ADN, la translocación de fosfatidilserina, la expresión de caspasas 3/7 y la pérdida de permeabilidad de la membrana. Los CEM-AB se aislaron, caracterizaron y utilizaron para los ensayos inmunológicos. Tras la activación de linfocitos humanos con perlas anti- CD3/anti-CD28, los CEM-AB no indujeron una inmunosupresión directa, en comparación con controles de células viables. Sin embargo, el pre-condicionamiento de monocitos/macrófagos humanos CD14+ con CEM-AB indujo un fenotipo M2 y desencadenó un potente efecto inhibidor de la proliferación de linfocitos (>90%). El tratamiento con cuerpos apoptóticos también indujo la sobreexpresión de moléculas de punto de control inmunológico y la secreción diferencial de factores de crecimiento. En conjunto, estos hallazgos sugieren que los CEM-AB mejoran la acción inmunosupresora preexistente de las CEM, confiriendo a los macrófagos un fenotipo M2 durante la inflamación. (Texto tomado de la fuente) |
dc.description.abstract | Immunotherapies based on mesenchymal stromal cells (MSC) represent tools for the treatment of inflammatory diseases. However, their clinical application is currently challenging. The biodistribution of MSC appears to be poor, which promotes the activation of apoptosis and the release of apoptotic bodies (AB). Since an interaction between MSCderived AB (MSC-AB) and components of the immune system has recently been proposed, in this project we demonstrated that MSC-AB exert synergistic immunomodulatory effects in in-vitro models of inflammation. For this purpose, MSC were obtained from Wharton's gelatin (WJ) by a disaggregation process. Exposure to gamma irradiation (25Gy) effectively induced apoptosis; as demonstrated by DNA fragmentation, phosphatidylserine translocation, caspases 3/7 expression and loss of membrane permeability. MSC-AB were isolated, characterized and used for immunological assays. Upon activation of human lymphocytes with anti-CD3/anti-CD28 beads, MSC-AB did not induce direct immunosuppression compared to viable cell controls. However, preconditioning of CD14+ human monocytes/macrophages with MSC-AB induced an M2 phenotype and triggered a potent inhibitory effect on lymphocyte proliferation (>90%). Treatment with apoptotic bodies also induced overexpression of immune checkpoint molecules and differential secretion of growth factors. Taken together, these findings suggest that MSC-AB enhance the preexisting immunosuppressive action of MSC by conferring an M2 phenotype to macrophages during inflammation. |
dc.format.extent | ix, 77 páginas |
dc.format.mimetype | application/pdf |
dc.language.iso | spa |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.subject.ddc | 570 - Biología |
dc.title | Evaluación del efecto inmunomodulador de los cuerpos apoptóticos de células estromales mesenquimales de Gelatina de Wharton |
dc.type | Trabajo de grado - Maestría |
dc.type.driver | info:eu-repo/semantics/masterThesis |
dc.type.version | info:eu-repo/semantics/acceptedVersion |
dc.publisher.program | Bogotá - Medicina - Maestría en Inmunología |
dc.contributor.researchgroup | Unidad de Terapias Avanzadas IDCBIS |
dc.description.degreelevel | Maestría |
dc.description.researcharea | Terapias avanzadas |
dc.identifier.instname | Universidad Nacional de Colombia |
dc.identifier.reponame | Repositorio Institucional Universidad Nacional de Colombia |
dc.identifier.repourl | https://repositorio.unal.edu.co/ |
dc.publisher.faculty | Facultad de Medicina |
dc.publisher.place | Bogotá - Colombia |
dc.publisher.branch | Universidad Nacional de Colombia - Sede Bogotá |
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dc.rights.accessrights | info:eu-repo/semantics/openAccess |
dc.subject.lemb | Inflamación |
dc.subject.lemb | Inflammation |
dc.subject.lemb | Técnicas inmunológicas |
dc.subject.lemb | Immunological techniques |
dc.subject.proposal | Células estromales mesenquimales |
dc.subject.proposal | Cuerpos apoptóticos |
dc.subject.proposal | Inmunomodulación |
dc.subject.proposal | Macrófagos |
dc.subject.proposal | Linfocitos |
dc.title.translated | Evaluation of the immunomodulatory effect of apoptotic bodies of Wharton's jelly mesenchymal stromal stromal cells |
dc.type.coar | http://purl.org/coar/resource_type/c_bdcc |
dc.type.coarversion | http://purl.org/coar/version/c_ab4af688f83e57aa |
dc.type.content | Text |
dc.type.redcol | http://purl.org/redcol/resource_type/TM |
oaire.accessrights | http://purl.org/coar/access_right/c_abf2 |
oaire.fundername | Instituto Distrital de Ciencia, Biotecnologia e Innovación en Salud |
dcterms.audience.professionaldevelopment | Estudiantes |
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