18 research outputs found
Fundamentals for modelling the airway wall:Interplay between cells, extracellular matrix, dimensionality, architecture and mechanics in the lung
Full text linkOur body, organs and tissues are made up of cells that are held together by a sort of glue called the extracellular matrix (ECM). In this three-dimensional environment the cells stick together and to the ECM. Mechanical properties of the ECM such as stiffness determine the fate and function of the bound cells. Therefore, it may come as no surprise that changes in the ECM’s composition and stiffness have an adverse effect on the organ’s function that is composed of the cells. This thesis showed that during chronic obstructive pulmonary disease, a lethal disease without cure, the cross-talk between cells and ECM is disrupted. We developed threedimensional culture models to understand fibroblasts i.e. cells from the connective tissue of main lung and airway cells are affected by ECM from healthy and diseased lungs as well as by varying stiffnesses. As it appears, higher than normal ECM stiffnesses promote airway disease. Our results pave the way for the development of novel therapies to treat COPD by targeting the derailed ECM
Chronic lung pathologies that require repair and regeneration.
Full text linkChronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, are a major cause of mortality worldwide. With the increasing incidence with ageing, the full impact of these diseases is yet to be realised. For most chronic lung diseases there are limited treatments options, with the existing approaches mainly addressing symptom relief. Little progress has been made, in recent years, in the development of new therapeutic strategies for managing these burdensome pathologies. There is an urgent need to increase our understanding of the mechanisms underlying these diseases. Endogenous progenitor cells (stem cells) have been recognised in many organs, including the lungs where they are suggested to maintain a population of cells that are able to facilitate the endogenous repair processes. Emerging knowledge of how these repair processes are disrupted in chronic lung diseases and the potential to capitalise upon the regenerative capacity of stem cell populations raise the hopes of the field worldwide for innovative treatment approaches for these devastating diseases in the future. This chapter outlines the series of diseases that may benefit from these emerging new therapeutic outlooks
Chronic lung pathologies that require repair and regeneration.
Full text linkChronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, are a major cause of mortality worldwide. With the increasing incidence with ageing, the full impact of these diseases is yet to be realised. For most chronic lung diseases there are limited treatments options, with the existing approaches mainly addressing symptom relief. Little progress has been made, in recent years, in the development of new therapeutic strategies for managing these burdensome pathologies. There is an urgent need to increase our understanding of the mechanisms underlying these diseases. Endogenous progenitor cells (stem cells) have been recognised in many organs, including the lungs where they are suggested to maintain a population of cells that are able to facilitate the endogenous repair processes. Emerging knowledge of how these repair processes are disrupted in chronic lung diseases and the potential to capitalise upon the regenerative capacity of stem cell populations raise the hopes of the field worldwide for innovative treatment approaches for these devastating diseases in the future. This chapter outlines the series of diseases that may benefit from these emerging new therapeutic outlooks
Chronic lung pathologies that require repair and regeneration.
Full text linkChronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, are a major cause of mortality worldwide. With the increasing incidence with ageing, the full impact of these diseases is yet to be realised. For most chronic lung diseases there are limited treatments options, with the existing approaches mainly addressing symptom relief. Little progress has been made, in recent years, in the development of new therapeutic strategies for managing these burdensome pathologies. There is an urgent need to increase our understanding of the mechanisms underlying these diseases. Endogenous progenitor cells (stem cells) have been recognised in many organs, including the lungs where they are suggested to maintain a population of cells that are able to facilitate the endogenous repair processes. Emerging knowledge of how these repair processes are disrupted in chronic lung diseases and the potential to capitalise upon the regenerative capacity of stem cell populations raise the hopes of the field worldwide for innovative treatment approaches for these devastating diseases in the future. This chapter outlines the series of diseases that may benefit from these emerging new therapeutic outlooks
Chronic lung pathologies that require repair and regeneration.
No full textChronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, are a major cause of mortality worldwide. With the increasing incidence with ageing, the full impact of these diseases is yet to be realised. For most chronic lung diseases there are limited treatments options, with the existing approaches mainly addressing symptom relief. Little progress has been made, in recent years, in the development of new therapeutic strategies for managing these burdensome pathologies. There is an urgent need to increase our understanding of the mechanisms underlying these diseases. Endogenous progenitor cells (stem cells) have been recognised in many organs, including the lungs where they are suggested to maintain a population of cells that are able to facilitate the endogenous repair processes. Emerging knowledge of how these repair processes are disrupted in chronic lung diseases and the potential to capitalise upon the regenerative capacity of stem cell populations raise the hopes of the field worldwide for innovative treatment approaches for these devastating diseases in the future. This chapter outlines the series of diseases that may benefit from these emerging new therapeutic outlooks
Higher Chain Length Distribution in Debranched Type-3 Resistant Starches (RS3) Increases TLR Signaling and Supports Dendritic Cell Cytokine Production
Full text linkScope: Resistant starches (RSs) are classically considered to elicit health benefits through fermentation. However, it is recently shown that RSs can also support health by direct immune interactions. Therefore, it has been hypothesized that the structural traits of RSs might impact the health benefits associated with their consumption. Methods and results: Effects of crystallinity, molecular weight, and chain length distribution of RSs are determined on immune Toll-like receptors (TLRs), dendritic cells (DCs), and T-cell cytokines production. To this end, four type-3 RSs (RS3) are compared, namely Paselli WFR, JD150, debranched Etenia, and Amylose fraction V, which are extracted from potatoes and enzymatically modified. Dextrose equivalent seems to be the most important feature influencing immune signaling via activation of TLRs. TLR2 and TLR4 are most strongly stimulated. Especially Paselli WFR is a potent activator of multiple receptors. Moreover, the presence of amylose, even to residual levels, enhances DC and T-cell cytokine responses. Paselli WFR and Amylose fraction V influence T-cell polarization. Conclusions: It has been shown here that chain length and particularly dextrose equivalent are critical features for immune activation. This knowledge might lead to tailoring and design of immune-active RS formulations.</p
Modulation of Biomaterial-Associated Fibrosis by Means of Combined Physicochemical Material Properties
Full text linkBiomaterial-associated fibrosis remains a significant challenge in medical implants. To optimize implant design, understanding the interplay between biomaterials and host cells during the foreign body response (FBR) is crucial. Material properties are known to influence cellular behavior and can be used to manipulate cell responses, but predicting the right combination for the desired outcomes is challenging. This study explores how combined physicochemical material properties impact early myofibroblast differentiation using the Biomaterial Advanced Cell Screening (BiomACS) technology, which assesses hundreds of combinations of surface topography, stiffness, and wettability in a single experiment. Normal human dermal fibroblasts (NHDFs) are screened for cell density, area, and myofibroblast markers α-smooth muscle actin (α-SMA) and Collagen type I (COL1) after 24 h and 7 days of culture, with or without transforming growth factor-beta (TGF-β). Results demonstrated that material properties influence fibroblast behavior after 7 days with TGF-β stimulation, with wettability emerging as the predominant factor, followed by stiffness. The study identified regions with increased cell adhesion while minimizing myofibroblast differentiation, offering the potential for implant surface optimization to prevent fibrosis. This research provides a powerful tool for cell-material studies and represents a critical step toward enhancing implant properties and reducing complications, ultimately improving patient outcomes.</p
