2026-06-28T20:33:43Zhttps://docta.ucm.es/rest/oai/requestoai:docta.ucm.es:20.500.14352/1366402026-05-11T23:56:25Zcom_20.500.14352_14col_20.500.14352_22
Docta Complutense
advisor
Fernández Gutiérrez, Benjamín
author
González Guede, Irene
2026-05-11T10:10:23Z
2026-05-11T10:10:23Z
2026-05-11
https://hdl.handle.net/20.500.14352/136640
La artrosis (OA) es una enfermedad articular de elevada prevalencia, sincura conocida, que supone una elevada carga clínica y socioeconómica. A pesarde los avances en el campo, aún no se dispone de modelos in vitro e in vivo capacesde reproducir con precisión la complejidad del tejido osteocondral humano. Esteestudio aborda dos necesidades en el contexto de la artrosis, el desarrollo de unmodelo de estudio fisiológicamente relevante para la OA y la investigación dedeterminadas alteraciones moleculares implicadas en la enfermedad. Por ello, elobjetivo es validar una plataforma microfluídica, Osteocondral Tissue-On-a-Chip,desarrollada con tejido osteocondral humano artrósico, que represente fielmentelas características fisiopatológicas de la enfermedad y la funcionalidad del tejidoosteocondral. Además, a partir del análisis de plasma y células madremesenquimales derivadas de médula ósea (BM-MSCs) de pacientes con OA, asícomo durante su diferenciación osteogénica in vitro, se investigan alteraciones enlos glipicanos (GPC1-6) y Notum. Especificamente, Notum es un regulador negativode la vía Wnt, que se encuentra aumentada en la OA. Por ello, se plantea inyectarNotum en el Osteocondral Tissue-On-a-Chip para evaluar si su intervencióncontribuye a restaurar el equilibrio tisular...Osteoarthritis (OA) is a highly prevalent joint disease with no known cure anda high clinical and socioeconomic burden. Despite advances in the field, in vitro andin vivo models capable of accurately reproducing the complexity of humanosteochondral tissue are not yet available. This study addresses two needs in thecontext of osteoarthritis, the development of a physiologically relevant model for OAresearch and the investigation of specific molecular alterations involved in thedisease. Therefore, the objective is to validate a microfluidic platform,Osteochondral Tissue-On-a-Chip, developed using human osteoarthriticosteochondral tissue, which faithfully represents the pathophysiologicalcharacteristics of the disease and the functionality of osteochondral tissue.Additionally, by analyzing plasma and bone marrow-derived mesenchymal stemcells (BM‑MSCs) from OA patients, as well as during their in vitro osteogenicdifferentiation, we investigate alterations in glypicans (GPC1–6) and Notum.Specifically, Notum is a negative regulator of Wnt signaling, a pathway known to beupregulated in OA. Accordingly, we propose administering Notum into theOsteochondral Tissue‑On‑a‑Chip to evaluate whether its intervention contributes torestore tissue balance...
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
Validación del modelo osteocondral tissue-on-a-chip y estudio de glipicanos y notum en la artrosis
doctoral thesis
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URL
https://docta.ucm.es/bitstreams/32475697-ad28-493a-9735-0d40bf5093f4/download
File
MD5
40515e109c6fe8e4f83d92533d87eeed
4684862
application/pdf
T46220.pdf