This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics... more This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
Mesenchymal stromal/progenitor cells (MSCs) are promising for cartilage cell-based therapies due ... more Mesenchymal stromal/progenitor cells (MSCs) are promising for cartilage cell-based therapies due to their differentiation capacity. However, MSCs can become senescent duringin vitroexpansion, a state characterized by stable cell cycle arrest, metabolic alterations, and substantial changes in the gene expression and secretory profile of the cell. In this study, we aimed to investigate how senescence and the senescence associated secretory phenotype (SASP) affect chondrogenic differentiation of MSCs. To study the effect of senescence, we exposed MSCs to gamma irradiation during expansion or during chondrogenic differentiation (pellet culture). When senescence was induced during expansion or at day-7 of chondrogenic differentiation, we observed a significant reduction in cartilage matrix. Interestingly, when senescence was induced at day-14 of differentiation, chondrogenesis was not significantly altered. Moreover, exposing chondrogenic pellets to medium conditioned by senescent pellet...
Background Without the availability of disease-modifying drugs, there is an unmet therapeutic nee... more Background Without the availability of disease-modifying drugs, there is an unmet therapeutic need for osteoarthritic patients. During osteoarthritis, the homeostasis of articular chondrocytes is dysregulated and a phenotypical transition called hypertrophy occurs, leading to cartilage degeneration. Targeting this phenotypic transition has emerged as a potential therapeutic strategy. Chondrocyte phenotype maintenance and switch are controlled by an intricate network of intracellular factors, each influenced by a myriad of feedback mechanisms, making it challenging to intuitively predict treatment outcomes, while in silico modeling can help unravel that complexity. In this study, we aim to develop a virtual articular chondrocyte to guide experiments in order to rationalize the identification of potential drug targets via screening of combination therapies through computational modeling and simulations. Results We developed a signal transduction network model using knowledge-based and...
Objective Inflammation is known to negatively affect cartilage repair. However, it is unclear how... more Objective Inflammation is known to negatively affect cartilage repair. However, it is unclear how inflammation influences the migration of mesenchymal stromal cells (MSCs) from the underlying bone marrow into the defect. We therefore aimed to investigate how synovial inflammation influences MSC migration, and whether modulation of inflammation with triamcinolone acetonide (TAA) may influence migration. Design Inflamed human osteoarthritic synovium, M(IFNγ+TNFα) pro-inflammatory macrophages, M(IL4) repair macrophages, M(IL10) anti-inflammatory macrophages, or synovial fibroblasts were cultured with/without TAA. Conditioned medium (CM) was harvested after 24 hours, and the effect on MSC migration was studied using a Boyden chamber assay. Inflammation was evaluated with gene expression and flow cytometry analysis. Results Synovium CM increased MSC migration. Modulation of synovial inflammation with TAA further increased migration 1.5-fold ( P < 0.01). TAA significantly decreased TNF...
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics... more This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
Mesenchymal stromal/progenitor cells (MSCs) are promising for cartilage cell-based therapies due ... more Mesenchymal stromal/progenitor cells (MSCs) are promising for cartilage cell-based therapies due to their differentiation capacity. However, MSCs can become senescent duringin vitroexpansion, a state characterized by stable cell cycle arrest, metabolic alterations, and substantial changes in the gene expression and secretory profile of the cell. In this study, we aimed to investigate how senescence and the senescence associated secretory phenotype (SASP) affect chondrogenic differentiation of MSCs. To study the effect of senescence, we exposed MSCs to gamma irradiation during expansion or during chondrogenic differentiation (pellet culture). When senescence was induced during expansion or at day-7 of chondrogenic differentiation, we observed a significant reduction in cartilage matrix. Interestingly, when senescence was induced at day-14 of differentiation, chondrogenesis was not significantly altered. Moreover, exposing chondrogenic pellets to medium conditioned by senescent pellet...
Background Without the availability of disease-modifying drugs, there is an unmet therapeutic nee... more Background Without the availability of disease-modifying drugs, there is an unmet therapeutic need for osteoarthritic patients. During osteoarthritis, the homeostasis of articular chondrocytes is dysregulated and a phenotypical transition called hypertrophy occurs, leading to cartilage degeneration. Targeting this phenotypic transition has emerged as a potential therapeutic strategy. Chondrocyte phenotype maintenance and switch are controlled by an intricate network of intracellular factors, each influenced by a myriad of feedback mechanisms, making it challenging to intuitively predict treatment outcomes, while in silico modeling can help unravel that complexity. In this study, we aim to develop a virtual articular chondrocyte to guide experiments in order to rationalize the identification of potential drug targets via screening of combination therapies through computational modeling and simulations. Results We developed a signal transduction network model using knowledge-based and...
Objective Inflammation is known to negatively affect cartilage repair. However, it is unclear how... more Objective Inflammation is known to negatively affect cartilage repair. However, it is unclear how inflammation influences the migration of mesenchymal stromal cells (MSCs) from the underlying bone marrow into the defect. We therefore aimed to investigate how synovial inflammation influences MSC migration, and whether modulation of inflammation with triamcinolone acetonide (TAA) may influence migration. Design Inflamed human osteoarthritic synovium, M(IFNγ+TNFα) pro-inflammatory macrophages, M(IL4) repair macrophages, M(IL10) anti-inflammatory macrophages, or synovial fibroblasts were cultured with/without TAA. Conditioned medium (CM) was harvested after 24 hours, and the effect on MSC migration was studied using a Boyden chamber assay. Inflammation was evaluated with gene expression and flow cytometry analysis. Results Synovium CM increased MSC migration. Modulation of synovial inflammation with TAA further increased migration 1.5-fold ( P < 0.01). TAA significantly decreased TNF...
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