Dendritic Cells: Location, Function, and Clinical Implications

Dendritic cells (DCs) are antigen-presenting cells derived from bone marrow precursors and form a widely distributed cellular system throughout the body. DCs exert immune-surveillance for exogenous and endogenous antigens and the later activation of naive T lymphocytes giving rise to various immunological responses. Different growth factors and cytokines can modulate the differentiation and function of DCs, GM-CSF, M-CSF, Flt3, and TGF-β, resulting in a large variety of DCs with different functional abilities. Thus, DCs are classified as plasmacytoid DCs (pDCs), conventional DCs (cDCs), and DCs derived from monocytes (mDCs). Functionally, the cDCs may be divided into two states: immature and mature. Immature DCs are specialist in uptaking and processing antigens; in contrast, mature DCs are professional in antigen presentation. It has been observed that immature cDCs can induce immune tolerance while mature cDCs may induce Th2 or Th1 immune responses. It is worth noting that different subpopulations of DCs have the ability to secrete different cytokine patterns, resulting in the induction of different immunological responses. Furthermore DCs are involved in the pathophysiology of several diseases such as contact hypersensitivity, autoimmune diseases, or cancer, but they can also be used as therapeutic tools in these conditions

Cellulose-Chitosan-Nanohydroxyapatite Hybrid Composites by One-Pot Synthesis for Biomedical Applications

The development of organic–inorganic hybrid materials deserves special interest for bone tissue engineering applications, where materials must have properties that induce the survival and activation of cells derived from the mesenchyme. In this work, four bio-nanocomposites based on cellulose and variable content of chitosan, from 15 to 50 w% based on cellulose, with nanohydroxyapatite and β-Glycerophosphate as cross-linking agent were synthesized by simplified and low-energy-demanding solvent exchange method to determine the best ratio of chitosan to cellulose matrix. This study analyzes the metabolic activity and survival of human dermal fibroblast cells cultivated in four bio-nanocomposites based on cellulose and the variable content of chitosan. The biocompatibility was tested by the in vitro cytotoxicity assays Live/Dead and PrestoBlue. In addition, the composites were characterized by FTIR, XRD and SEM. The results have shown that the vibration bands of β-Glycerophosphate have prevailed over the other components bands, while new diffraction planes have emerged from the interaction between the cross-linking agent and the biopolymers. The bio-nanocomposite micrographs have shown no surface porosity as purposely designed. On the other hand, cell death and detachment were observed when the composites of 1 and 0.1 w/v% were used. However, the composite containing 10 w% chitosan, against the sum of cellulose and β-Glycerophosphate, has shown less cell death and detachment when used at 0.01 w/v%, making it suitable for more in vitro studies in bone tissue engineering, as a promising economical biomaterial

GK-1 Improves the Immune Response Induced by Bone Marrow Dendritic Cells Loaded with MAGE-AX in Mice with Melanoma

The aim of dendritic cell (DC) vaccination in cancer is to induce tumor-specific effector T cells that may reduce and control tumor mass. Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response. GK-1 peptide, derived from Taenia crassiceps, induces not only increase in TNFα, IFNγ, and MCP-1 production in cocultures of DCs and T lymphocytes but also immunological protection against influenza virus. Moreover, the aim of this investigation is the use of GK-1 as a bone marrow DCs (BMDCs) immunostimulant targeted with MAGE antigen; thus, BMDC may be used as immunotherapy against murine melanoma. GK-1 induced in BMDCs a meaningful increment of CD86 and IL-12. In addition, the use of BMDCs TNFα/GK-1/MAGE-AX induced the highest survival and the smallest tumors in mice. Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes. Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment. These results highlight the properties of GK-1 as an immunostimulant of DCs and suggest as a potential candidate the use of this immunotherapy against cancer disease

Gelatin/Hyaluronic Acid Scaffold Coupled to CpG and MAGE-A5 as a Treatment against Murine Melanoma

The half-time of cells and molecules used in immunotherapy is limited. Scaffolds-based immunotherapy against cancer may increase the half-life of the molecules and also support the migration and activation of leukocytes in situ. For this purpose, the use of gelatin (Ge)/hyaluronic acid (HA) scaffolds coupled to CpG and the tumor antigen MAGE-A5 is proposed. Ge and HA are components of the extracellular matrix that stimulate cell adhesion and activation of leucocytes; CpG can promote dendritic cell maturation, and MAGE-A5 a specific antitumor response. C57BL/6 mice were treated with Ge/HA/scaffolds coupled to MAGE-A5 and/or CpG and then challenged with the B16-F10 melanoma cell line. Survival, tumor growth rate and the immune response induced by the scaffolds were analyzed. Ge/HA/CpG and Ge/HA/MAGE-A5 mediated dendritic cell maturation and macrophage activation, increased survival, and decreased the tumor growth rate and a tumor parenchyma with abundant cell death areas and abundant tumor cells with melanin granules. Only the scaffolds coupled to MAGE-A5 induced the activation of CD8 T cells. In conclusion, Ge/HA scaffolds coupled to CpG or MAGE-A5, but not the mixture, can induce a successful immune response capable of promoting tumor cell clearance and increased survival

The mitochondrial alternative oxidase Aox1 is needed to cope with respiratory stress but dispensable for pathogenic development in <i>Ustilago maydis</i>

<div><p>The mitochondrial alternative oxidase is an important enzyme that allows respiratory activity and the functioning of the Krebs cycle upon disturbance of the respiration chain. It works as a security valve in transferring excessive electrons to oxygen, thereby preventing potential damage by the generation of harmful radicals. A clear biological function, besides the stress response, has so far convincingly only been shown for plants that use the alternative oxidase to generate heat to distribute volatiles. In fungi it was described that the alternative oxidase is needed for pathogenicity. Here, we investigate expression and function of the alternative oxidase at different stages of the life cycle of the corn pathogen <i>Ustilago maydis</i> (Aox1). Interestingly, expression of Aox1 is specifically induced during the stationary phase suggesting a role at high cell density when nutrients become limiting. Studying deletion strains as well as overexpressing strains revealed that Aox1 is dispensable for normal growth, for cell morphology, for response to temperature stress as well as for filamentous growth and plant pathogenicity. However, during conditions eliciting respiratory stress yeast-like growth as well as hyphal growth is strongly affected. We conclude that Aox1 is dispensable for the normal biology of the fungus but specifically needed to cope with respiratory stress.</p></div

Differential adhesion and fibrinolytic activity of mesenchymal stem cells from human bone marrow, placenta, and Wharton’s jelly cultured in a fibrin hydrogel

Mesenchymal stem cells isolated from different tissues should share associated markers and the capability to differentiate to mesodermal lineages. However, their behavior varies in specific microenvironments. Herein, adhesion and fibrinolytic activity of mesenchymal stem cells from placenta, bone marrow, and Wharton’s jelly were evaluated in fibrin hydrogels prepared with nonpurified blood plasma and compared with two-dimensional cultures. Despite the source, mesenchymal stem cells adhered through focal adhesions positive for vinculin and integrin αV in two dimensions, while focal adhesions could not be detected in fibrin hydrogels. Moreover, some cells could not spread and stay rounded. The proportions of elongated and round phenotypes varied, with placenta mesenchymal stem cells having the lowest percentage of elongated cells (~10%). Mesenchymal stem cells degraded fibrin at distinct rates, and placenta mesenchymal stem cells had the strongest fibrinolytic activity, which was achieved principally through the plasminogen–plasmin axis. These findings might have clinical implications in tissue engineering and wound healing therapy

Effect of Aox1 on the sporidia growth of <i>U</i>. <i>maydis</i> and sensitivity to temperature.

<p><b>A)</b> Budding of yeast cells. Sporidia of FB2 (wt), FB2aox1Δ, FB2aox1-Gfp, and FB2Potef:aox1-Gfp. <b>B)</b> Time course of cell growth in rich medium as measured by the absorbance at 600 nm. <b>C)</b> Effect of temperature on the growth of sporidia. Growth plates with 1:5 dilutions (starting with OD = 0.5).</p