Publication: Regeneración e inmunomodulación en células madre mesquenquimales de pacientes artrósicos: estudio genético y funcional
Loading...
Files
Official URL
Full text at PDC
Publication Date
2014-11-19
Authors
Advisors (or tutors)
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Universidad Complutense de Madrid
Citations
Exportar
Abstract
La artrosis es una enfermedad musculoesquelética causada por un desequilibrio entre factores catabólicos y anabólicos que desemboca en la pérdida del cartílago articular, la inflamación sinovial y cambios en el hueso subcondral. En la actualidad no existe ningún tratamiento farmacológico efectivo, más allá del alivio del dolor, para el tratamiento de la artrosis, y en cualquier caso no se logra una recuperación de los tejidos de la articulación dañada. En este contexto, las propiedades de autorenovación, pluripotencialidad e inmunomodulación de las células madre mesenquimales (CMMs) aplicadas mediante las nuevas terapias celulares son esperanzadoras. No obstante, tanto si las células son utilizadas de forma autóloga como alogénica, es necesario determinar cómo la propia patología puede limitar el potencial terapéutico de estas células. En este estudio, se usó un micrroarray de ADN para analizar las diferencias transcripcionales en las CMMs de pacientes con artrosis y sujetos control sin artrosis con el fin de analizar las características de las CMMs con la vista puesta en su uso terapias celulares. En las CMMs de artrosis se encontraron regulados a la baja genes relacionados con la capacidad regenerativa de las CMMs, en concreto, el gen COL10A1 y la ruta de señalización IGF1. Además se encontraron asociaciones genéticas entre SNPs de estos genes y artrosis, rs11965969 en el caso de COL10A1 y rs35767 en el caso de IGF1 en la población española. Por otro lado, no se encontraron diferencias significativas en los genes relacionados con la capacidad inmunomoduladora de las CMMs entre ambos grupos analizados. Se realizó un estudio complementario sobre la inmunomodulación de las CMMs en pacientes artrósicos, donde observamos que las CMMs de estos pacientes conservan la capacidad de responder a factores proinflamatorios, incluso tras varias semanas en cultivo in vitro en una matriz de alginato, abriendo así las expectativas de aplicación de este sistema en enfermedades con un componente inflamatorio como es la artrosis.
Osteoarthritis is a musculoskeletal disease caused by an imbalance between catabolic and anabolic factors, which leads to articular cartilage loss, sinovial inflammation and subchondral bone changes. Up to date, there is not effective drug treatment for osteoarthritis, beyond a pain relief. Anyway, the regeneration of tissues from the damaged joint is not achieved. In this context, the application of mesenchymal stem cells (MSCs), given their capacities of self-renewal, pluripontency and immunomodulation, could be hopeful. Nevertheless, both, in autologous or allogenic MSCs therapies, it should be necessary to determine wether in a pathologic environment, such as osteoarthritis, these properties are altered limiting the therapeutic potential of these cells. Aiming to determine the suitability of MSCs in cell therapies, in this study a DNA microarray was used to comparatively describe the transcriptional differences between MSCs, obtained from osteoarthritic patients, and those from non-OA donors. Interestingly, we found a downregulated expression of genes essential for the regenerative potential maintenance in OA-MSCs; in particular, in COL10A1 gene and in genes involved in the IGF1 signaling pathway. Moreover, we also found an OA genetic association, in spanish population, with single nucleotide polymorphisms in the COL10A1 and IGF1 genes. On the other hand, in the analyzed MSCs, no significant differences were found with regard to immunomodulation related genes. Furthermore, we performed an immunomodulation study on osteoarthritic MSCs, where we observed that MSCs maintained their capacity to respond to proinflammatory factors. Indeed, after several weeks on in vitro culture, MSCs embedded in an alginate matrix, maintained their inmunomodulatory properties. These results are promising for the future application of MSCs in localized inflammatory diseases, such as osteoarthritis.
Osteoarthritis is a musculoskeletal disease caused by an imbalance between catabolic and anabolic factors, which leads to articular cartilage loss, sinovial inflammation and subchondral bone changes. Up to date, there is not effective drug treatment for osteoarthritis, beyond a pain relief. Anyway, the regeneration of tissues from the damaged joint is not achieved. In this context, the application of mesenchymal stem cells (MSCs), given their capacities of self-renewal, pluripontency and immunomodulation, could be hopeful. Nevertheless, both, in autologous or allogenic MSCs therapies, it should be necessary to determine wether in a pathologic environment, such as osteoarthritis, these properties are altered limiting the therapeutic potential of these cells. Aiming to determine the suitability of MSCs in cell therapies, in this study a DNA microarray was used to comparatively describe the transcriptional differences between MSCs, obtained from osteoarthritic patients, and those from non-OA donors. Interestingly, we found a downregulated expression of genes essential for the regenerative potential maintenance in OA-MSCs; in particular, in COL10A1 gene and in genes involved in the IGF1 signaling pathway. Moreover, we also found an OA genetic association, in spanish population, with single nucleotide polymorphisms in the COL10A1 and IGF1 genes. On the other hand, in the analyzed MSCs, no significant differences were found with regard to immunomodulation related genes. Furthermore, we performed an immunomodulation study on osteoarthritic MSCs, where we observed that MSCs maintained their capacity to respond to proinflammatory factors. Indeed, after several weeks on in vitro culture, MSCs embedded in an alginate matrix, maintained their inmunomodulatory properties. These results are promising for the future application of MSCs in localized inflammatory diseases, such as osteoarthritis.
Description
Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída el 29-04-2014