Chronic lung diseases:entangled in extracellular matrix

The extracellular matrix (ECM) is the scaffold that provides structure and support to all organs, including the lung; however, it is also much more than this. The ECM provides biochemical and biomechanical cues to cells that reside or transit through this micro-environment, instructing their responses. The ECM structure and composition changes in chronic lung diseases; how such changes impact disease pathogenesis is not as well understood. Cells bind to the ECM through surface receptors, of which the integrin family is one of the most widely recognised. The signals that cells receive from the ECM regulate their attachment, proliferation, differentiation, inflammatory secretory profile and survival. There is extensive evidence documenting changes in the composition and amount of ECM in diseased lung tissues. However, changes in the topographical arrangement, organisation of the structural fibres and stiffness (or viscoelasticity) of the matrix in which cells are embedded have an undervalued but strong impact on cell phenotype. The ECM in diseased lungs also changes in physical and biomechanical ways that drive cellular responses. The characteristics of these environments alter cell behaviour and potentially orchestrate perpetuation of lung diseases. Future therapies should target ECM remodelling as much as the underlying culprit cells

Interaction of different cell types with magnesium modified by plasma electrolytic oxidation

Magnesium (Mg) is a material widely used in industrial applications due to its low weight, ductility, and excellent mechanical properties. For non-permanent implants, Mg is particularly well-suited because of its biodegradability, while its degradation products are not harmful. However, Mg is chemically reactive, and cytotoxic hydrogen gas is released as part of the degradation. This adverse degradation can be tuned using plasma electrolytic oxidation (PEO). With PEO, a surface layer of MgO/Mg(OH)(2) is deposited on the surface of Mg in a controlled way. The electrolytes used during PEO influence the surface's chemistry and topography and thus expectedly the biological response of adhered cells. In this study, thin samples of commercial pure of Mg (c.p Mg) were modified by PEO guided by different electrolytes, and the biological activity was assessed on vascular cells, immune cells, and repair cells (adipose tissue-derived stromal cells, ASCs). Vascular cells were more vulnerable than ASCs for compounds released by surface-coated Mg. All surface coatings supported the proliferation of adhered ASC. Released compounds from surface-coated Mg delayed but did not block in vitro wound closure of fibroblasts monolayers. Preformed endothelial tubes were vulnerable for released compounds, while their supporting ASC was not. We conclude that PEO-based surface-coating of Mg supports adhesion and future delivery of therapeutic vascular repair cells such as ASC, but that the observed vulnerability of vascular cells for coated Mg components warrants investigations in vivo

Adipose Tissue-Derived Components:From Cells to Tissue Glue to Treat Dermal Damage

In recent decades, adipose tissue transplantation has become an essential treatment modality for tissue (volume) restoration and regeneration. The regenerative application of adipose tissue has only recently proven its usefulness; for example, the method is useful in reducing dermal scarring and accelerating skin-wound healing. The therapeutic effect is ascribed to the tissue stromal vascular fraction (tSVF) in adipose tissue. This consists of stromal cells, the trophic factors they secrete and the extracellular matrix (ECM), which have immune-modulating, pro-angiogenic and anti-fibrotic properties. This concise review focused on dermal regeneration using the following adipose-tissue components: adipose-tissue-derived stromal cells (ASCs), their secreted trophic factors (ASCs secretome), and the ECM. The opportunities of using a therapeutically functional scaffold, composed of a decellularized ECM hydrogel loaded with trophic factors of ASCs, to enhance wound healing are explored as well. An ECM-based hydrogel loaded with trophic factors combines all regenerative components of adipose tissue, while averting the possible disadvantages of the therapeutic use of adipose tissue, e.g., the necessity of liposuction procedures with a (small) risk of complications, the impossibility of interpatient use, and the limited storage options.</p

Improved corrosion resistance of commercially pure magnesium after its modification by plasma electrolytic oxidation with organic additives

The optimal mechanical properties render magnesium widely used in industrial and biomedical applications. However, magnesium is highly reactive and unstable in aqueous solutions, which can be modulated to increase stability of reactive metals that include the use of alloys or by altering the surface with coatings. Plasma electrolytic oxidation is an efficient and tuneable method to apply a surface coating. By varying the plasma electrolytic oxidation parameters voltage, current density, time and (additives in the) electrolytic solution, the morphology, composition and surface energy of surface coatings are set. In the present study, we evaluated the influence on surface coatings of two solute additives, i.e. hexamethylenetetramine and mannitol, to base solutes silicate and potassium hydroxide. Results from in vitro studies in NaCl demonstrated an improvement in the corrosion resistance. In addition, coatings were obtained by a two-step anodization procedure, firstly anodizing in an electrolyte solution containing sodium fluoride and secondly in an electrolyte solution with hexamethylenetetramine and mannitol, respectively. Results showed that the first layer acts as a protective layer which improves the corrosion resistance in comparison with the samples with a single anodizing step. In conclusion, these coatings are promising candidates to be used in biomedical applications in particular because the components are non-toxic for the body and the rate of degradation of the surface coating is lower than that of pure magnesium

Towards standardization of human adipose-derived stromal cells secretomes

The secretome of adipose-derived stromal cells (ASC) is a heterogeneous mixture of components with a beneficial influence on cellular microenvironments. As such, it represents a cell-free alternative in regenerative medicine therapies. Pathophysiological conditions increase the therapeutic capacity of ASC and, with this, the benefits of the secretome. Such conditions can be partially mimicked in vitro by adjusting culturing conditions. Secretomics, the unbiased analysis of a cell secretome by mass spectrometry, is a powerful tool to describe the composition of ASC secretomes. In this proteomics databases review, we compared ASC secretomic studies to retrieve persistently reported proteins resulting from the most explored types of culturing conditions used in research, i.e., exposure to normoxia, hypoxia, or cytokines. Our comparisons identified only eight common proteins within ASC normoxic secretomes, no commonalities within hypoxic ASC secretomes, and only nine within secretomes of ASC exposed to proinflammatory cytokines. Within these, and regardless of the culturing condition that stimulated secretion, a consistent presence of extracellular matrix-related pathways associated with such proteins was identified. Confounders such as donors' age, sex, body mass index, the anatomical area where ASC were harvested, secretome collection method, data description, and how the data is shared with the scientific community are discussed as factors that might explain our outcomes. We conclude that standardization is imperative as the currently available ASC secretomic studies do not facilitate solid conclusions on the therapeutic value of different ASC secretomes.</p

Towards standardization of human adipose-derived stromal cells secretomes

The secretome of adipose-derived stromal cells (ASC) is a heterogeneous mixture of components with a beneficial influence on cellular microenvironments. As such, it represents a cell-free alternative in regenerative medicine therapies. Pathophysiological conditions increase the therapeutic capacity of ASC and, with this, the benefits of the secretome. Such conditions can be partially mimicked in vitro by adjusting culturing conditions. Secretomics, the unbiased analysis of a cell secretome by mass spectrometry, is a powerful tool to describe the composition of ASC secretomes. In this proteomics databases review, we compared ASC secretomic studies to retrieve persistently reported proteins resulting from the most explored types of culturing conditions used in research, i.e., exposure to normoxia, hypoxia, or cytokines. Our comparisons identified only eight common proteins within ASC normoxic secretomes, no commonalities within hypoxic ASC secretomes, and only nine within secretomes of ASC exposed to proinflammatory cytokines. Within these, and regardless of the culturing condition that stimulated secretion, a consistent presence of extracellular matrix-related pathways associated with such proteins was identified. Confounders such as donors' age, sex, body mass index, the anatomical area where ASC were harvested, secretome collection method, data description, and how the data is shared with the scientific community are discussed as factors that might explain our outcomes. We conclude that standardization is imperative as the currently available ASC secretomic studies do not facilitate solid conclusions on the therapeutic value of different ASC secretomes.</p