Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis

We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis

Computational modeling of biomagnetic micropolar blood flow and heat transfer in a two-dimensional non-Darcian porous medium

We study theoretically and computationally the incompressible, non-conducting, micropolar, biomagnetic (blood) flow and heat transfer through a two-dimensional square porous medium in an (x,y) coordinate system, bound by impermeable walls. The magnetic field acting on the fluid is generated by an electrical current flowing normal to the x–y plane, at a distance l beneath the base side of the square. The flow regime is affected by the magnetization B 0 and a linear relation is used to define the relationship between magnetization and magnetic field intensity. The steady governing equations for x-direction translational (linear) momentum, y-direction translational (linear) momentum, angular momentum (micro-rotation) and energy (heat) conservation are presented. The energy equation incorporates a special term designating the thermal power per unit volume due to the magnetocaloric effect. The governing equations are non-dimensionalized into a dimensionless (ξ,η) coordinate system using a set of similarity transformations. The resulting two point boundary value problem is shown to be represented by five dependent non-dimensional variables, f ξ (velocity), f η (velocity), g (micro-rotation), E (magnetic field intensity) and θ (temperature) with appropriate boundary conditions at the walls. The thermophysical parameters controlling the flow are the micropolar parameter (R), biomagnetic parameter (N H ), Darcy number (Da), Forchheimer (Fs), magnetic field strength parameter (Mn), Eckert number (Ec) and Prandtl number (Pr). Numerical solutions are obtained using the finite element method and also the finite difference method for Ec=2.476×10−6 and Prandtl number Pr=20, which represent realistic biomagnetic hemodynamic and heat transfer scenarios. Temperatures are shown to be considerably increased with Mn values but depressed by a rise in biomagnetic parameter (N H ) and also a rise in micropolarity (R). Translational velocity components are found to decrease substantially with micropolarity (R), a trend consistent with Newtonian blood flows. Micro-rotation values are shown to increase considerably with a rise in R values but are reduced with a rise in biomagnetic parameter (N H ). Both translational velocities are boosted with a rise in Darcy number as is micro-rotation. Forchheimer number is also shown to decrease translational velocities but increase micro-rotation. Excellent agreement is demonstrated between both numerical solutions. The mathematical model finds applications in blood flow control devices, hemodynamics in porous biomaterials and also biomagnetic flows in highly perfused skeletal tissue

The Marine-Derived Filamentous Fungi in Biotechnology

For a long time considered as essentially terrestrial organisms, filamentous fungi have recently disclosed to be widespread in marine habitats. Such a pervasiveness not only concerns obligate marine species but also a multitude of taxa known from disparate terrestrial substrates whose occurrence at sea, at first considered incidental, is now regarded as an evidence of extreme ecological flexibility. Actually, the peculiar physico-chemical properties of the marine environment are presumed to have induced special physiological adaptations that could be considered in view of a possible biotechnological exploitation of fungal strains recovered from marine sources. The potential of filamentous fungi reported from marine contexts for the manifold applications in biotechnology involving microbial strains is revised in this chapter

The systemic nature of CKD

International audienceThe accurate definition and staging of chronic kidney disease (CKD) is one of the major achievements of modern nephrology. Intensive research is now being undertaken to unravel the risk factors and pathophysiologic underpinnings of this disease. In particular, the relationships between the kidney and other organs have been comprehensively investigated in experimental and clinical studies in the last two decades. Owing to technological and analytical limitations, these links have been studied with a reductionist approach focusing on two organs at a time, such as the heart and the kidney or the bone and the kidney. Here, we discuss studies that highlight the complex and systemic nature of CKD. Energy balance, innate immunity and neuroendocrine signalling are highly integrated biological phenomena. The diseased kidney disrupts such integration and generates a high-risk phenotype with a clinical profile encompassing inflammation, protein-energy wasting, altered function of the autonomic and central nervous systems and cardiopulmonary, vascular and bone diseases. A systems biology approach to CKD using omics techniques will hopefully enable in-depth study of the pathophysiology of this systemic disease, and has the potential to unravel critical pathways that can be targeted for CKD prevention and therapy