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Desarrollo de un modelo in vitro de deficiencia constitutiva de la enzima GALNS en células estromales mesenquimales humanas mediante el uso de CRISPR-Cas9
dc.rights.license | Atribución-NoComercial-SinDerivadas 4.0 Internacional |
dc.contributor.advisor | Salguero López, Gustavo Andrés |
dc.contributor.advisor | Dueñas Gómez, Zulma Janeth |
dc.contributor.author | Dorsant Ardón, Valérie |
dc.date.accessioned | 2022-08-23T16:03:42Z |
dc.date.available | 2022-08-23T16:03:42Z |
dc.date.issued | 2022-08-19 |
dc.identifier.uri | https://repositorio.unal.edu.co/handle/unal/82024 |
dc.description.abstract | La mucopolisacaridosis Tipo IVA o síndrome de Morquio es una enfermedad autosómica recesiva causada por la deficiencia de la enzima N galactosamina -6- sulfatasa (GALNS), necesaria para descomponer los glucosaminoglicanos (GAG) queratán sulfato (KS) y condroitín sulfato (CS). La deficiencia enzimática conlleva a la disfunción lisosomal especialmente en tejidos conectivos ricos en KS y CS como cartílago, córnea y válvulas cardiacas. Existe evidencia acumulada in vitro e in vivo que aborda los mecanismos fisiopatológicos que determinan finalmente las manifestaciones clínicas en pacientes afectados, especialmente en tejidos osteocondrales. Sin embargo, la dificultad en la obtención de tejidos óseos y articulares de pacientes afectados ha limitado el estudio de los efectos deletéreos tempranos de la deficiencia de GALNS en el componente estromal mesenquimal. Específicamente es poco conocido el efecto de la pérdida de la de GALNS el potencial proliferativo y de diferenciación osteogénica de estas células. Para este estudio se emplearon CEM de gelatina de Wharton (GW) de cordón umbilical, las cuales han sido ampliamente estudiadas en el grupo de investigación de la Unidad de Terapias Avanzadas del IDCBIS, estas fueron editadas mediante el uso de CRISPR-Cas9 para la generación de células knock-out, y se determinó compromiso en su capacidad proliferativa, y de diferenciación osteogénica asociada al porcentaje predicho de edición génica. (Texto tomada de la fuente) |
dc.description.abstract | Mucopolysaccharidoses type IVA or Morquio's disease is a pathology with a recessive inheritance pattern due to the deficiency of the N-galactosamine-6-sulfatase enzyme (GALNS), required for the metabolism of the glycosaminoglycans (GAG) Keratan sulfate (KS) and Chondroitin Sulfate (CS). The enzyme deficiency leads to lysosomal dysfunction that affects primarily CS and KS rich tissues like cartilage, cornea, and heart valves. There is increasing in vivo and in vitro evidence that describes the physio pathological mechanisms that lead to the clinical presentation in these patients especially in osteochondral tissues. However, it is difficult to obtain biopsy samples of bone and articular cartilage from these patients, and this limits the study of the early pathological signs due to GALNS deficiency in mesenchymal stromal cells (MSC). For this study MSCs from Wharton jelly were used, these cells have been broadly studied in the Advanced Therapies Unit Group at IDCBIS, these cells were edited using CRISP-Cas9 to generate a knockout for the GALNS gene, and a negative effect in proliferation and differentiation was found in association of the predicted gene editing percentage of the cellular pool. |
dc.format.extent | 71 páginas |
dc.format.mimetype | application/pdf |
dc.language.iso | spa |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.subject.ddc | 570 - Biología::576 - Genética y evolución |
dc.subject.other | Pruebas de Mutagenicidad |
dc.subject.other | Mutagenicity Tests |
dc.subject.other | Células Madre Mesenquimatosas |
dc.subject.other | Mesenchymal Stem Cells |
dc.title | Desarrollo de un modelo in vitro de deficiencia constitutiva de la enzima GALNS en células estromales mesenquimales humanas mediante el uso de CRISPR-Cas9 |
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 Genética Humana |
dc.contributor.researchgroup | Unidad de Terapias Avanzadas – Instituto Distrital de Ciencia Biotecnología e Innovación (IDCBIS) |
dc.description.degreelevel | Maestría |
dc.description.degreename | Magíster en Genética Humana |
dc.description.researcharea | Ingeniería Molecular y Celular |
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.department | Departamento de Morfología |
dc.publisher.faculty | Facultad de Medicina |
dc.publisher.place | Bogotá, Colombia |
dc.publisher.branch | Universidad Nacional de Colombia - Sede Bogotá |
dc.relation.indexed | RedCol |
dc.relation.indexed | LaReferencia |
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dc.rights.accessrights | info:eu-repo/semantics/openAccess |
dc.subject.proposal | Células estromales mesenquimales |
dc.subject.proposal | Proteína 9 asociada a CRISPR |
dc.subject.proposal | Edición génica |
dc.subject.proposal | Mucopolisacaridosis tipo IV A |
dc.subject.proposal | Enfermedad de Morquio |
dc.subject.proposal | Mesenchymal stromal cells |
dc.subject.proposal | CRISPR-Associated Protein 9 |
dc.subject.proposal | Gene edition |
dc.subject.proposal | Mucopolysaccharidoses type VI A |
dc.subject.proposal | Morquio’s disease |
dc.title.translated | Development of an in vitro model of the GALNS enzyme deficiency in human mesenchymal stromal cells using the CRISPR/Cas9 system |
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 |
dcterms.audience.professionaldevelopment | Investigadores |
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