Striatal compartmentalization and clustering of different subtypes of astrocytes is altered in the zQ175 Huntington′s disease mouse model

Huntington′s disease (HD) is a devastating neurodegenerative disease that primarily affects the striatum, a brain region that controls movement and some forms of cognition. Dysfunction and loss of medium spiny neurons of the striatum is accompanied by astrogliosis (increased astrocyte density and pathology). For decades, astrocytes were considered a homogeneous cell type, but recent transcriptomic analyses revealed astrocytes are a heterogeneous population classified into multiple subtypes depending on the expression of different gene markers. Here, we studied whether three different striatal astrocyte subtypes expressing glutamine synthetase (GS), glial fibrillary acidic protein (GFAP), or S100 calcium-binding protein B (S100B) are differentially altered in HD. We conducted a comparative immunofluorescence analysis in the striatum of WT and the heterozygous zQ175 HD mouse model and found that the expression and abundance of GFAP+ and S100B+ astrocytes increased in zQ175 mice, while GS+ astrocytes showed no alteration. We then explored whether there was a differential spatial distribution of any of these subtypes within the striatum. We developed a systematic brain compartmentalization approach and found that while GS+ and S100B+ astrocytes were more homogeneously distributed throughout the striatum in zQ175 mice, GFAP+ astrocytes preferentially accumulated in the dorsomedial and dorsolateral striatum, which are regions associated with goal-directed and habitual behaviors. Additionally, GFAP+ astrocytes in zQ175 mice showed increased clustering, a parameter that indicates increased proximity and that is associated with localized inflammation and/or neurodegeneration. Our data suggest a differential susceptibility in both increased density and striatal compartmentalization of different subtypes of astrocytes in zQ175. These results highlight new potential implications for our understanding of astrocyte pathology in HD.

An optimized 3D-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications

A clinical implementation of cell-based bone regeneration in combination with scaffold materials requires the development of efficient, controlled and reproducible seeding procedures and a tailor-made bioreactor design. A perfusion system for efficient, homogeneous, and rapid seeding with human adipogenic stem cells in bone substitute scaffolds was designed. Variants concerning medium inlet and outlet port geometry, i.e. cylindrical or conical diffuser, cell concentration, perfusion mode and perfusion rates were simulated in silico. Cell distribution during perfusion was monitored by dynamic [18F]FDG micro-PET/CT and validated by laser scanning microscopy with three-dimensional image reconstruction. By iterative feedback of the in silico and in vitro experiments, the homogeneity of cell distribution throughout the scaffold was optimized with adjustment of flow rates, cell density and perfusion properties. Finally, a bioreactor with a conical diffusor geometry was developed, that allows a homogeneous cell seeding (hoover coefficient: 0.24) in less than 60 min with an oscillating perfusion mode. During this short period of time, the cells initially adhere within the entire scaffold and stay viable. After two weeks, the formation of several cell layers was observed, which was associated with an osteogenic differentiation process. This newly designed bioreactor may be considered as a prototype for chairside application.

Tip-Viscid Electrohydrodynamic Jet 3D Printing of Composite Osteochondral Scaffold

A novel method called tip-viscid electrohydrodynamic jet printing (TVEJ), which produces a viscous needle tip jet, was presented to fabricate a 3D composite osteochondral scaffold with controllability of fiber size and space to promote cartilage regeneration. The tip-viscid process, by harnessing the combined effects of thermal, flow, and electric fields, was first systematically investigated by simulation analysis. The influences of process parameters on printing modes and resolutions were investigated to quantitatively guide the fabrication of various structures. 3D architectures with high aspect ratio and good interlaminar bonding were printed, thanks to the stable fine jet and its predictable viscosity. 3D composite osteochondral scaffolds with controllability of architectural features were fabricated, facilitating ingrowth of cells, and eventually inducing homogeneous cell proliferation. The scaffold’s properties, which included chemical composition, wettability, and durability, were also investigated. Feasibility of the 3D scaffold for cartilage tissue regeneration was also proven by in vitro cellular activities.

Improving the Hydrophilicity of Flexible Polyurethane Foams with Sodium Acrylate Polymer

Hydrophilic, flexible polyurethane (FPU) foams made from Hypol prepolymers are capable of retaining large amounts of water and saline solutions. The addition of different catalysts and surfactant agents to Hypol JM 5008 prepolymer was assayed to obtain a foam with good structural stability and elasticity. The combination of three catalysts, stannous octoate and two amine-based ones (Tegoamin 33 and Tegoamin BDE), and the surfactant Niax silicone L-620LV allowed to synthesize a foam with a homogeneous cell size distribution, exhibiting the highest saline absorption capacity (2.4 g/gram of foam) and almost complete shape recovery, with up to a 20% of remaining deformation. Then, superabsorbent sodium acrylate polymer (PNaA) was added to the FPU foam up to 8 pph. The urine absorption capacity of the foam was increased about 24.8% by incorporating 6 pph of PNaA, absorbing 17.46 g of saline solution per foam gram, without any negative impact on the rest of the foam properties. All these properties make the synthesized foams suitable for corporal fluids absorption applications in which elasticity and low-density are required.

Tailoring Epoxy Resin Foams by Pre-Curing with Neat Amine Hardeners and Its Derived Carbamates

The use of amine-based carbamates with their dual function, acting as amine curing agents and CO2 blowing agents after their decomposition without by-products, are promising for ecofriendly epoxy foams as high-performance materials. However, controlling cell morphology requires a proper adjustment of the viscosity at the foaming step. The viscosity is altered not only by blending neat amine and its derived carbamate at a fixed pre-curing time, but also by changing the pre-curing time at a fixed blend ratio. Within this study, diglycidylether of bisphenol A (DGEBA) epoxy resin is mixed with different blend ratios of isophorone diamine (IPDA) and its derived carbamate (B-IPDA). The systems are characterized by DSC and rheology experiments to identify the pre-curing effects on the derived epoxy foams. Epoxy foams at a blend ratio of 30/70w IPDA/B-IPDA showed the best foam morphology and an optimum Tg compared to other blend ratios. Furthermore, it was found that both pre-curing times, 2 h and 3 h, for the 30/70w IPDA/B-IPDA system reveal a more homogeneous cell structure. The study proves that the blending of neat amine and carbamate is beneficial for the foaming performance of carbamate systems.

An intercrypt subpopulation of goblet cells is essential for colonic mucus barrier function

The intestinal mucus layer, an important element of epithelial protection, is produced by goblet cells. Intestinal goblet cells are assumed to be a homogeneous cell type. In this study, however, we delineated their specific gene and protein expression profiles and identified several distinct goblet cell populations that form two differentiation trajectories. One distinct subtype, the intercrypt goblet cells (icGCs), located at the colonic luminal surface, produced mucus with properties that differed from the mucus secreted by crypt-residing goblet cells. Mice with defective icGCs had increased sensitivity to chemically induced colitis and manifested spontaneous colitis with age. Furthermore, alterations in mucus and reduced numbers of icGCs were observed in patients with both active and remissive ulcerative colitis, which highlights the importance of icGCs in maintaining functional protection of the epithelium.

Neutrophils in COVID-19

Strong evidence has been accumulated since the beginning of the COVID-19 pandemic that neutrophils play an important role in the pathophysiology, particularly in those with severe disease courses. While originally considered to be a rather homogeneous cell type, recent attention to neutrophils has uncovered their fascinating transcriptional and functional diversity as well as their developmental trajectories. These new findings are important to better understand the many facets of neutrophil involvement not only in COVID-19 but also many other acute or chronic inflammatory diseases, both communicable and non-communicable. Here, we highlight the observed immune deviation of neutrophils in COVID-19 and summarize several promising therapeutic attempts to precisely target neutrophils and their reactivity in patients with COVID-19.

Segregation of brain and organizer precursors is differentially regulated by Nodal signaling at blastula stage

ABSTRACTThe blastula Chordin- and Noggin-expressing (BCNE) center comprises animal-dorsal and marginal-dorsal cells of the amphibian blastula and contains the precursors of the brain and the gastrula organizer. Previous findings suggested that the BCNE behaves as a homogeneous cell population that only depends on nuclear β-catenin activity but does not require Nodal and later segregates into its descendants during gastrulation. In contrast to previous findings, in this work, we show that the BCNE does not behave as a homogeneous cell population in response to Nodal antagonists. In fact, we found that chordin.1 expression in a marginal subpopulation of notochordal precursors indeed requires Nodal input. We also establish that an animal BCNE subpopulation of cells that express both, chordin.1 and sox2 (a marker of pluripotent neuroectodermal cells), and gives rise to most of the brain, persisted at blastula stage after blocking Nodal. Therefore, Nodal signaling is required to define a population of chordin.1+ cells and to restrict the recruitment of brain precursors within the BCNE as early as at blastula stage. We discuss our findings in Xenopus in comparison to other vertebrate models, uncovering similitudes in early brain induction and delimitation through Nodal signaling.This article has an associated First Person interview with the first author of the paper.

Variations of In-Plane Mechanical Properties of Cellular Structures With Different Hierarchical Organizations

Inspired by the nature, this study analyzes in-plane compressive responses of different modes of hierarchical architected structures with varying topologies. Architected cellular structures with two different unit cell topologies — square and kagome are considered, both having a relative density of 0.25. Each unit cell topology is designed with three different configurations. The base structure is the primitive one with solid homogeneous cell wall. The nested hierarchical structure is derived from the primitive one with cellular structuring in the cell wall. The third and final one is the fractal-like hierarchical structure, where same unit cells appear on different length scales. 3D printed structures were subjected to uniaxial compression to characterize their in-plane mechanical properties. The compressive stress-strain behaviors reveal that all the structures demonstrate the classical behavior of cellular structures followed by significant recovery of their initial shape upon load withdrawal. The energy absorptions demonstrated by the plateau regions before densification are not only governed by their structural topologies, but also largely governed by the configurations of hierarchical organizations. Hence, this study suggests the application specific design of hierarchical architected structures for defined loading conditions.