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

Effect of cattle trampling and farm machinery traffic on soil compaction of an Entic Haplustoll in a semiarid region of Argentina

Soil compaction has detrimental effects on the physical, mechanical and hydraulic properties of soils, and affects important soil processes and function, and crop productivity. This work was conducted to investigate soil compaction impacts in integrated arable croppinglivestock systems managed under conventional tillage (CT) and no-tillage (NT). The work examined the combined effects of cattle trampling and farm machinery traffic on: soil strength, soil deformation, and water infiltration into soil. The following treatments were applied to soil (Entic Haplustoll, 60% sand) managed under CT and NT: three traffic intensities (1, 5, 7 passes) performed with light (2WD, 53 kN) and heavy (4WD, 100.4 kN) tractors, and two stocking densities (400 and 700 kg ha-1 ), respectively. Controls were also used to represent the condition of the soil without any effect of livestock or field traffic. In both tillage systems, soil penetration resistance (strength) increased and water infiltration into soil decreased as traffic intensities or stocking rates applied increased. There was a significant traffic intensity × stocking rate interaction, which influenced the depth and extent of soil compaction at depth. Despite these results, stubble grazing during fallow should not be discouraged as this practice offers mixed farming systems several agronomic and financial benefits. If stubble was to be grazed, the system would need to be carefully managed: (1) avoid ‘random’ traffic using permanent or semipermanent traffic paths to minimise the field wheeled area, (2) vacate livestock from the field, or confine it to a sacrificial area, when the soil water content exceeds a critical level above which soil damage is likely, and (3) maintain more than 60%–70% ground cover. Tillage repair treatments can be targeted to those sacrificial or ‘hot-spots’ areas so that localised, as supposed to widespread, compaction problems are rectified before the next crop is established

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

Three-dimensionally two-photon lithography realized vascular grafts

Generation of artificial vascular grafts as blood vessel substitutes is a primary challenge in biomaterial and tissue-engineering research. Ideally, these grafts should be able to recapitulate physiological and mechanical properties of natural vessels and guide the assembly of an endothelial cell lining to ensure hemo-compatibility. In this paper, we advance on this challenging task by designing and fabricating 3D vessel analogues by two-photon laser lithography using a synthetic photoresist. These scaffolds guarantee human endothelial cell adhesion and proliferation, and proper elastic behavior to withstand the pressure exerted by blood flow