Synthetic/ECM-inspired hybrid platform for hollow microcarriers with ROS-triggered nanoporation hallmarks

Reactive oxygen species (ROS) are key pathological signals expressed in inflammatory diseases such as cancer, ischemic conditions and atherosclerosis. An ideal drug delivery system should not only be responsive to these signals but also should not elicit an unfavourable host response. This study presents an innovative platform for drug delivery where a natural/synthetic composite system composed of collagen type I and a synthesized polythioether, ensures a dual stimuli-responsive behaviour. Collagen type I is an extracellular matrix constituent protein, responsive to matrix metalloproteinases (MMP) cleavage per se. Polythioethers are stable synthetic polymers characterized by the presence of sulphur, which undergoes a ROS-responsive swelling switch. A polythioether was synthesised, functionalized and tested for cytotoxicity. Optimal conditions to fabricate a composite natural/synthetic hollow sphere construct were optimised by a template-based method. Collagen-polythioether hollow spheres were fabricated, revealing uniform size and ROS-triggered nanoporation features. Cellular metabolic activity of H9C2 cardiomyoblasts remained unaffected upon exposure to the spheres. Our natural/synthetic hollow microspheres exhibit the potential for use as a pathological stimuli-responsive reservoir system for applications in inflammatory diseases

A worm gel-based 3D model to elucidate the paracrine interaction between multiple myeloma and mesenchymal stem cells

Multiple myeloma (MM) is a malignancy of terminally-differentiated plasma cells that develops mainly inside the bone marrow (BM) microenvironment. It is well known that autocrine and paracrine signals are responsible for the progression of this disease but the precise mechanism and contributions from single cell remain largely unknown. Mesenchymal stem cells (MSC) are an important cellular component of the BM: they support MM growth by increasing its survival and chemo-resistance, but little is known about the paracrine signaling pathways. Three-dimensional (3D) models of MM-MSC paracrine interactions are much more biologically-relevant than simple 2D models and are considered essential for detailed studies of MM pathogenesis. Herein we present a novel 3D co-culture model designed to mimic the paracrine interaction between MSC and MM cells. MSC were embedded within a previously characterized thermoresponsive block copolymer worm gel that can induce stasis in human pluripotent stem cells (hPSC) and then co-cultured with MM cells. Transcriptional phenotyping of co-cultured cells indicated the dysregulation of genes that code for known disease-relevant factors, and also revealed IL-6 and IL-10 as upstream regulators. Importantly, we have identified a synergistic paracrine signaling pathway between IL-6 and IL-10 that plays a critical role in sustaining MM cell proliferation. Our findings indicate that this 3D co-culture system is a useful model to investigate the paracrine interaction between MM cells and the BM microenvironment in vitro. This approach has revealed a new mechanism that promotes the proliferation of MM cells and suggested a new therapeutic target

A worm gel-based 3D model to elucidate the paracrine interaction between multiple myeloma and mesenchymal stem cells

Multiple myeloma (MM) is a malignancy of terminally-differentiated plasma cells that develops mainly inside the bone marrow (BM) microenvironment. It is well known that autocrine and paracrine signals are responsible for the progression of this disease but the precise mechanism and contributions from single cell remain largely unknown. Mesenchymal stem cells (MSC) are an important cellular component of the BM: they support MM growth by increasing its survival and chemo-resistance, but little is known about the paracrine signaling pathways. Three-dimensional (3D) models of MM-MSC paracrine interactions are much more biologically-relevant than simple 2D models and are considered essential for detailed studies of MM pathogenesis. Herein we present a novel 3D co-culture model designed to mimic the paracrine interaction between MSC and MM cells. MSC were embedded within a previously characterized thermoresponsive block copolymer worm gel that can induce stasis in human pluripotent stem cells (hPSC) and then co-cultured with MM cells. Transcriptional phenotyping of co-cultured cells indicated the dysregulation of genes that code for known disease-relevant factors, and also revealed IL-6 and IL-10 as upstream regulators. Importantly, we have identified a synergistic paracrine signaling pathway between IL-6 and IL-10 that plays a critical role in sustaining MM cell proliferation. Our findings indicate that this 3D co-culture system is a useful model to investigate the paracrine interaction between MM cells and the BM microenvironment in vitro. This approach has revealed a new mechanism that promotes the proliferation of MM cells and suggested a new therapeutic target

Does a life cycle assessment remain valid after 20 years? Scenario analysis with a bus stop study

Purpose: The goal of this article is to find out if an old Life Cycle Assessment (LCA) study remains valid or not after a period of time. To answer this we re-perform an LCA of a bus stop in the city of Barcelona that was performed about 20 years ago. Methods: The LCA of a bus stop, performed and published in 1998, is re-performed and its results compared with those of the original study, keeping the same scope of the original system. The software used by the original study was SimaPro; the data came from IVAM LCA data, BUWAL 250, IDEMAT 96 and PRe4 databases; and CML 1992 impact assessment methodology was used. The new study used thinkstep GaBi6 software; GaBi6 Professional + extension databases; and CML 2001 methodology. The assessment includes an analysis of the key influencing factors that cause the discrepancies, such as models and databases. Moreover, a specific focus on evolution of the methodologies and its influence on the results is described. A 30% of difference between results is accepted as the threshold value to be able to state that the results differ. Results and discussion: The overall results obtained in the two studies are quite similar or, at least, comparable. However, when analysing and comparing the systems disaggregated stage by stage, higher differences in each impact category are found. Therefore, the lower discrepancy at system level may be due to coincidence or compensation. The main causes of discrepancy have been found to be: (i) the update of the assessment methodologies and characterization factors, (ii) the improvement of the databases, and (iii) the change in the techno-sphere and the improvement of the environmental policies. Conclusions and recommendations: After 15–20 years, LCA results cannot be considered reliable. Results can, however, be used as an indication for the expected order of magnitude of the impacts and for the relative importance of the processes in the different life cycle stages. The comparison is made through one case study only; therefore, it can barely be used as a generalization, neither for the difference in results nor for the sources of discrepancy. Nevertheless, this type of analysis can be considered a first step in quantifying the longevity of LCA results. © 2019 Elsevier B.V