Is elevated gastric tissue NOX2 associated with lymphoma of mucosa-associated lymphoid tissue?

Abstract Helicobacter pylori infection plays a crucial role in the pathogenesis of gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). However, the host response to this infection is also important in the development of the disease. In particular, NADPH oxidases (NOXs) which generate reactive oxygen species are known to induce cell damage possibly leading to carcinogenesis. We analyze for the first time NOX expression in a series of well characterized gastric MALT lymphoma (GML) patients in comparison with controls. Our observation leads to the hypothesis that NOX2 expression is significantly associated with GML.     

Multi-cellularity in cardiac tissue engineering,how close are we to native heart tissue?

Journal of Muscle Research and Cell Motility - Tissue engineering is a complex field where the elements of biology and engineering are combined in an attempt to recapitulate the native environment...     

The role of protein solubilization in antigen removal from xenogeneic tissue for heart valve tissue engineering

Decellularization techniques have been developed in an attempt to reduce the antigenicity of xenogeneic biomaterials, a critical barrier in their use as tissue engineering scaffolds. However, numerous studies have demonstrated inadequate removal and subsequent persistence of antigens in the biomaterial following decellularization, resulting in an immune response upon implantation. Thus, methods to enhance antigen removal (AR) are critical for the use of xenogeneic biomaterials in tissue engineering and regenerative medicine. In the present study, AR methods incorporating protein solubilization principles were investigated for their ability to reduce antigenicity of bovine pericardium (BP) for heart valve tissue engineering. Bovine pericardium following AR (BP-AR) was assessed for residual antigenicity, tensile properties, and extracellular matrix composition. Increasing protein solubility during AR significantly decreased the residual antigenicity of BP-AR-by an additional 80% compared to hypotonic solution or 60% compared to 0.1% (w/v) SDS decellularization methods. Moreover, solubilizing agents have a dominant effect on reducing the level of residual antigenicity of BP-AR beyond that achieved by AR additives alone. Tested AR methods did not compromise the tensile properties of BP-AR compared to native BP. Furthermore, residual cell nuclei did not correlate to residual antigenicity, demonstrating that residual nuclei counts may not be an appropriate indicator of successful AR. In conclusion, AR strategies promoting protein solubilization significantly reduced residual antigens compared to decellularization methods without compromising biomaterial functional properties. This study demonstrates the importance of solubilizing protein antigens for their removal in the generation of xenogeneic scaffolds.     

Update on tissue renin–angiotensin systems

Angiotensin (Ang) II is not only generated in the circulation by renin and angiotensin-converting enzyme (ACE) but also is produced locally in numerous organs including kidney, vessels, heart, adrenal gland, eye, testis, and brain. Furthermore, widely distributed mast cells have been shown to be a production site. Local Ang II production process is commonly termed the result of a “tissue” renin–angiotensin system (RAS). Because pharmacological experiments do not easily allow targeting of specific tissues, many novel findings about the functional importance of tissue RAS have been collected from transgenic rodent models. These animals either overexpress or lack RAS components in specific tissues and thereby elucidate their local functions. The data to date show that in most tissues local RAS amplify the actions of circulating Ang II with important implications for physiology and pathophysiology of cardiovascular diseases. This review summarizes the recent findings on the importance of tissue RAS in the most relevant cardiovascular organs.     

Solid freeform fabrication of bone tissue engineering scaffolds

INTRODUCTION　　 Tissue engineering is a promising approach to large segmental bone repair fortrauma,replacement surgery,skeletal deficiency or abnormal development. Thefabrication of boneregeneration scaffoldswith appropriate bone conductive property,bone inductive property,biodegradation property and mechanical properties is thecrux of this approach. Traditional scaffold fabrication technologies include phaseseparation technology,salt-leaching technology and gas-induced foaming technolo-…     

TNFα-dependent development of lymphoid tissue in the absence of RORγt+ lymphoid tissue inducer cells

Lymphoid tissue often forms within sites of chronic inflammation. Here we report that expression of the proinflammatory cytokine tumor necrosis factor α (TNFα) drives development of lymphoid tissue in the intestine. Formation of this ectopic lymphoid tissue was not dependent on the presence of canonical RORgt⁺ lymphoid tissue–inducer (LTi) cells, because animals expressing increased levels of TNFα but lacking RORgt⁺ LTi cells (TNF/Rorc(gt)^−/− mice) developed lymphoid tissue in inflamed areas. Unexpectedly, such animals developed several lymph nodes (LNs) that were structurally and functionally similar to those of wild-type animals. TNFα production by F4/80⁺ myeloid cells present within the anlagen was important for the activation of stromal cells during the late stages of embryogenesis and for the activation of an organogenic program that allowed the development of LNs. Our results show that lymphoid tissue organogenesis can occur in the absence of LTi cells and suggest that interactions between TNFα-expressing myeloid cells and stromal cells have an important role in secondary lymphoid organ formation.     

Connective tissue: A body-wide signaling network?

Unspecialized "loose" connective tissue forms an anatomical network throughout the body. This paper presents the hypothesis that, in addition, connective tissue functions as a body-wide mechanosensitive signaling network. Three categories of signals are discussed: electrical, cellular and tissue remodeling, each potentially responsive to mechanical forces over different time scales. It is proposed that these types of signals generate dynamic, evolving patterns that interact with one another. Such connective tissue signaling would be affected by changes in movement and posture, and may be altered in pathological conditions (e.g. local decreased mobility due to injury or pain). Connective tissue thus may function as a previously unrecognized whole body communication system. Since connective tissue is intimately associated with all other tissues (e.g. lung, intestine), connective tissue signaling may coherently influence (and be influenced by) the normal or pathological function of a wide variety of organ systems. Demonstrating the existence of a connective signaling network therefore may profoundly influence our understanding of health and disease.     

Maxwell's equations-based dynamic laser–tissue interaction model

Since its invention in the early 1960s, the laser has been used as a tool for surgical, therapeutic, and diagnostic purposes. To achieve maximum effectiveness with the greatest margin of safety it is important to understand the mechanisms of light propagation through tissue and how that light affects living cells. Lasers with novel output characteristics for medical and military applications are too often implemented prior to proper evaluation with respect to tissue optical properties and human safety. Therefore, advances in computational models that describe light propagation and the cellular responses to laser exposure, without the use of animal models, are of considerable interest. Here, a physics-based laser–tissue interaction model was developed to predict the dynamic changes in the spatial and temporal temperature rise during laser exposure to biological tissues. Unlike conventional models, the new approach is grounded on the rigorous electromagnetic theory that accounts for wave interference, polarization, and nonlinearity in propagation using a Maxwell's equations-based technique.     

Tibolone: what does tissue specific activity mean?

Preclinical studies has found that tibolone can display a weak estrogenic, progestational and androgenic activity. The effect produced depends mainly on the target tissue involved. Clinical data indicate that tibolone produces the hormonal effects needed to treat climacteric symptoms and to prevent long-term effects of the menopause without stimulating breast and endometrial tissues. This clinical profile would be produced by the tissue specific activity of tibolone and its main metabolites. Tibolone's tissue specific activity may be explained by the interplay of several mechanisms, such as the metabolic conversion of tibolone to compounds with different biological activity, the classical interaction with the steroid receptor and the specific local metabolism, within the target tissue. Therefore, the tissue response and thus the clinical effect produced by tibolone in a given tissue seem to depend on the predominating mechanisms and interactions present in that tissue.     

Polyacrylamide phantom for self-actuating needle–tissue interaction studies

This study presents a polyacrylamide gel as a phantom material for needle insertion studies specifically developed for self-actuating needles to enhance the precise placement of needles in prostate. Bending of these self-actuating needles within tissue is achieved by Nitinol actuators attached to the needle body; however these actuators usually involve heating that can thermally damage the tissue surrounding the needles. Therefore, to develop and access feasibility of these needles, a polyacrylamide gel has been developed that mimics the thermal damage and mechanical properties of prostate tissue. Mechanical properties of the polyacrylamide gel was controlled by varying the concentrations of acrylamide monomer and N,N-methylene-bisacrylamide (BIS) cross-linker, and thermal sensitivity was achieved by adding bovine serum albumin (BSA) protein. Two polyacrylamide gels with different concentrations were developed to mimic the elastic modulus of the tissue. The two phantoms showed different rupture toughness and different deflection of bevel-tip needle. To study the thermal damage, a Nitinol wire was embedded in the phantom and resistively heated. The measured opaque zone (0.40 mm) formed around the wire was close to the estimated damage zone (0.43 mm) determined using the cumulative equivalent minutes at 43 °C.     

Can microcarrier-expanded chondrocytes synthesize cartilaginous tissue in vitro?

Tissue engineering is a promising approach for articular cartilage repair; however, it is challenging to produce adequate amounts of tissue in vitro from the limited number of cells that can be extracted from an individual. Relatively few cell expansion methods exist without the problems of de-differentiation and/or loss of potency. Recently, however, several studies have noted the benefits of three-dimensional (3D) over monolayer expansion, but the ability of 3D expanded chondrocytes to synthesize cartilaginous tissue constructs has not been demonstrated. Thus, the purpose of this study was to compare the properties of engineered cartilage constructs from expanded cells (monolayer and 3D microcarriers) to those developed from primary chondrocytes. Isolated bovine chondrocytes were grown for 3 weeks in either monolayer (T-Flasks) or 3D microcarrier (Cytodex 3) expansion culture. Expanded and isolated primary cells were then seeded in high density culture on Millicell? filters for 4 weeks to evaluate the ability to synthesize cartilaginous tissue. While microcarrier expansion was twice as effective as monolayer expansion (microcarrier: 110-fold increase, monolayer: 52-fold increase), the expanded cells (monolayer and 3D microcarrier) were not effectively able to synthesize cartilaginous tissue in vitro. Tissues developed from primary cells were substantially thicker and accumulated significantly more extracellular matrix (proteoglycan content: 156%-292% increase; collagen content: 70%-191% increase). These results were attributed to phenotypic changes experienced during the expansion phase. Monolayer expanded chondrocytes lost their native morphology within 1 week, whereas microcarrier-expanded cells were spreading by 3 weeks of expansion. While the use of 3D microcarriers can lead to large cellular yields, preservation of chondrogenic phenotype during expansion is required in order to synthesize cartilaginous tissue.     

Sol–gel silica-based biomaterials and bone tissue regeneration

The impact of bone diseases and trauma in developed and developing countries has increased significantly in the last decades. Bioactive glasses, especially silica-based materials, are called to play a fundamental role in this field due to their osteoconductive, osteoproductive and osteoinductive properties. In the last years, sol–gel processes and supramolecular chemistry of surfactants have been incorporated to the bioceramics field, allowing the porosity of bioglasses to be controlled at the nanometric scale. This advance has promoted a new generation of sol–gel bioactive glasses with applications such as drug delivery systems, as well as regenerative grafts with improved bioactive behaviour. Besides, the combination of silica-based glasses with organic components led to new organic–inorganic hybrid materials with improved mechanical properties. Finally, an effort has been made to organize at the macroscopic level the sol–gel glass preparation. This effort has resulted in new three-dimensional macroporous scaffolds, suitable to be used in tissue engineering techniques or as porous pieces to be implanted in situ. This review collects the most important advances in the field of silica glasses occurring in the last decade, which are called to play a lead role in the future of bone regenerative therapies.     

Biomimetic chitosan–nanohydroxyapatite composite scaffolds for bone tissue engineering

We describe a comparative assessment of the structure–property–process relationship of three-dimensional chitosan–nanohydroxyapatite (nHA) and pure chitosan scaffolds in conjunction with their respective biological response with the aim of advancing our insight into aspects that concern bone tissue engineering. High- and medium-molecular-weight (MW) chitosan scaffolds with 0.5, 1 and 2 wt.% fraction of nHA were fabricated by freezing and lyophilization. The nanocomposites were characterized by a highly porous structure and the pore size (～50 to 120 μm) was in a similar range for the scaffolds with different content of nHA. A combination of X-ray diffraction, Fourier transform infrared spectroscopy and electron microscopy indicated that nHA particles were uniformly dispersed in chitosan matrix and there was a chemical interaction between chitosan and nHA. The compression modulus of hydrated chitosan scaffolds was increased on the addition of 1 wt.% nHA from 6.0 to 9.2 kPa in high-MW scaffold. The water uptake ability of composites decreased with an increase in the amount of nHA, while the water retention ability was similar to pure chitosan scaffold. After 28 days in physiological condition, nanocomposites indicated about 10% lower degree of degradation in comparison to chitosan scaffold. The biological response of pre-osteoblasts (MC 3T3-E1) on nanocomposite scaffolds was superior in terms of improved cell attachment, higher proliferation, and well-spread morphology in relation to chitosan scaffold. In composite scaffolds, cell proliferation was about 1.5 times greater than pure chitosan after 7 days of culture and beyond, as implied by qualitative analysis via fluorescence microscopy and quantitative study through MTT assay. The observations related to well-developed structure morphology, physicochemical properties and superior cytocompatibility suggest that chitosan–nHA porous scaffolds are potential candidate materials for bone regeneration although it is necessary to further enhance the mechanical properties of the nanocomposite.     

Multifunctional silk–heparin biomaterials for vascular tissue engineering applications

Over the past 30 years, silk has been proposed for numerous biomedical applications that go beyond its traditional use as a suture material. Silk sutures are well tolerated in humans, but the use of silk for vascular engineering applications still requires extensive biocompatibility testing. Some studies have indicated a need to modify silk to yield a hemocompatible surface. This study examined the potential of low molecular weight heparin as a material for refining silk properties by acting as a carrier for vascular endothelial growth factor (VEGF) and improving silk hemocompatibility. Heparinized silk showed a controlled VEGF release over 6 days; the released VEGF was bioactive and supported the growth of human endothelial cells. Silk samples were then assessed using a humanized hemocompatibility system that employs whole blood and endothelial cells. The overall thrombogenic response for silk was very low and similar to the clinical reference material polytetrafluoroethylene. Despite an initial inflammatory response to silk, apparent as complement and leukocyte activation, the endothelium was maintained in a resting, anticoagulant state. The low thrombogenic response and the ability to control VEGF release support the further development of silk for vascular applications.