Murine iPSC-Loaded Scaffold Grafts Improve Bone Regeneration in Critical-Size Bone Defects.

In certain situations, bones do not heal completely after fracturing. One of these situations is a critical-size bone defect where the bone cannot heal spontaneously. In such a case, complex fracture treatment over a long period of time is required, which carries a relevant risk of complications. The common methods used, such as autologous and allogeneic grafts, do not always lead to successful treatment results. Current approaches to increasing bone formation to bridge the gap include the application of stem cells on the fracture side. While most studies investigated the use of mesenchymal stromal cells, less evidence exists about induced pluripotent stem cells (iPSC). In this study, we investigated the potential of mouse iPSC-loaded scaffolds and decellularized scaffolds containing extracellular matrix from iPSCs for treating critical-size bone defects in a mouse model. In vitro differentiation followed by Alizarin Red staining and quantitative reverse transcription polymerase chain reaction confirmed the osteogenic differentiation potential of the iPSCs lines. Subsequently, an in vivo trial using a mouse model (n = 12) for critical-size bone defect was conducted, in which a PLGA/aCaP osteoconductive scaffold was transplanted into the bone defect for 9 weeks. Three groups (each n = 4) were defined as (1) osteoconductive scaffold only (control), (2) iPSC-derived extracellular matrix seeded on a scaffold and (3) iPSC seeded on a scaffold. Micro-CT and histological analysis show that iPSCs grafted onto an osteoconductive scaffold followed by induction of osteogenic differentiation resulted in significantly higher bone volume 9 weeks after implantation than an osteoconductive scaffold alone. Transplantation of iPSC-seeded PLGA/aCaP scaffolds may improve bone regeneration in critical-size bone defects in mice.

Promoting Complex Problem Solving by Introducing Schema-Governed Categories of Key Causal Models.

The ability to recognize key causal models across situations is associated with expertise. The acquisition of schema-governed category knowledge of key causal models may underlie this ability. In an experimental study (n = 183), we investigated the effects of promoting the construction of schema-governed categories and how an enhanced ability to recognize the key causal models relates to performance in complex problem-solving tasks that are based on the key causal models. In a 2 × 2 design, we tested the effects of an adapted version of an intervention designed to build abstract mental representations of the key causal models and a tutorial designed to convey conceptual understanding of the key causal models and procedural knowledge. Participants who were enabled to recognize the underlying key causal models across situations as a result of the intervention and the tutorial (i.e., causal sorters) outperformed non-causal sorters in the subsequent complex problem-solving task. Causal sorters outperformed the control group, except for the subtask knowledge application in the experimental group that did not receive the tutorial and, hence, did not have the opportunity to elaborate their conceptual understanding of the key causal models. The findings highlight that being able to categorize novel situations according to their underlying key causal model alone is insufficient for enhancing the transfer of the according concept. Instead, for successful application, conceptual and procedural knowledge also seem to be necessary. By using a complex problem-solving task as the dependent variable for transfer, we extended the scope of the results to dynamic tasks that reflect some of the typical challenges of the 21st century.

Cell Type-Specific Anti-Adhesion Properties of Peritoneal Cell Treatment with Plasma-Activated Media (PAM).

Postoperative abdominal adhesions are responsible for serious clinical disorders. Administration of plasma-activated media (PAM) to cell type-specific modulated proliferation and protein biosynthesis is a promising therapeutic strategy to prevent pathological cell responses in the context of wound healing disorders. We analyzed PAM as a therapeutic option based on cell type-specific anti-adhesive responses. Primary human peritoneal fibroblasts and mesothelial cells were isolated, characterized and exposed to different PAM dosages. Cell type-specific PAM effects on different cell components were identified by contact- and marker-independent Raman imaging, followed by thorough validation by specific molecular biological methods. The investigation revealed cell type-specific molecular responses after PAM treatment, including significant cell growth retardation in peritoneal fibroblasts due to transient DNA damage, cell cycle arrest and apoptosis. We identified a therapeutic dose window wherein specifically pro-adhesive peritoneal fibroblasts were targeted, whereas peritoneal mesothelial cells retained their anti-adhesive potential of epithelial wound closure. Finally, we demonstrate that PAM treatment of peritoneal fibroblasts reduced the expression and secretion of pro-adhesive cytokines and extracellular matrix proteins. Altogether, we provide insights into biochemical PAM mechanisms which lead to cell type-specific pro-therapeutic cell responses. This may open the door for the prevention of pro-adhesive clinical disorders.

Investigation of the Morphology of Adrenal Glands in Hens Kept in Two Different Housing Systems-A Pilot Study.

It is difficult to objectively assess the chronic effects of housing systems on livestock and particularly on laying hens. However, this seems to be important in the context of animal welfare. Therefore, we conducted the present study in order to compare the effect of two different housing conditions, single cage (SC) and floor pen (FP), on the morphology of the adrenal gland. A higher amount of interrenal cells, which secrete stress hormones, can lead to a difference in the relation of adrenal and interrenal cells, which could be interpreted as an indication of chronic stress. For this purpose, adrenal glands were extracted, prepared, stained and examined by microscopy, and total area of the cut, total area of interrenal cells and total area of adrenal cells were measured. As a result, all laying hens had a higher percentage of interrenal cells than adrenal cells (FP: interrenal cells/adrenal cells = 78.37%/21.63%; SC: 80.00%/20.00%). The median of adrenal-interrenal ratio did not differ significantly (FP = 0.2503, SC = 0.2499), while the variation of the ratio between laying hens in FP and SC showed a slight tendency of a higher ratio in adrenal glands of FP (p < 0.0870). Body weight and adrenal-interrenal ratio were significantly negatively correlated in laying hens in FP (rS = -0.943, p < 0.0048) but not in SC (rS = -0.162, p = 0.7283). There was no significant correlation between body weight and total cell area for interrenal cells or adrenal cells. Body weight was significantly lower for laying hens kept in SC than for laying hens kept in FP (p < 0.0001). Due to the present results, it can be concluded that keeping laying hens in single cages can have a negative effect on body weight.

Increased IL-8 concentrations in the cerebrospinal fluid of patients with unipolar depression.

INTRODUCTION: Unipolar depression is a common and debilitating disorder. Immunological explanatory approaches have become increasingly important in recent years and can be studied particularly well in the cerebrospinal fluid (CSF). Previous studies discerned alterations in interleukin (IL)-6 and IL-8 levels; however, findings regarding IL-8 were partly contradictory. The aim of the present study was to investigate the concentrations of different cytokines and chemokines, focusing on IL-8, in the CSF of patients with unipolar depression. MATERIALS AND METHODS: Participants included 40 patients with unipolar depression and 39 mentally healthy controls with idiopathic intracranial hypertension. CSF cytokine levels were measured using a magnetic bead multiplexing immunoassay. RESULTS: IL-8 levels in the CSF of the patient group with depression were significantly higher than those in the control group (Mean ± SD: 38.44 ± 6.26 pg/ml versus 21.40 ± 7.96 pg/ml; p < .001). LIMITATIONS: The significance of the results is limited by the retrospective design and methodological aspects. DISCUSSION: The main findings of this study were significantly higher concentrations of IL-8 in the CSF of patients with unipolar depression than in the control group. The detection of high CSF IL-8 levels in this study supports the idea that inflammatory processes might play a role in the pathophysiology of a subgroup of patients with depression.