Akt1 signalling supports acinar proliferation and limits acinar-to-ductal metaplasia formation upon induction of acute pancreatitis.

Molecular signalling mediated by the phosphatidylinositol-3-kinase (PI3K)-Akt axis is a key regulator of cellular functions. Importantly, alteration of the PI3K-Akt signalling underlies the development of different human diseases, thus prompting the investigation of the pathway as a molecular target for pharmacologic intervention. In this regard, recent studies showed that small molecule inhibitors of PI3K, the upstream regulator of the pathway, reduced the development of inflammation during acute pancreatitis, a highly debilitating and potentially lethal disease.

ENDOXY - Development of a Biomimetic Oxygenator-Test-Device.

Objective: This study focusses on the development of a biomimetic oxygenator test device. Due to limited biocompatibility, current oxygenators do not allow mid- to long-term therapy. Tissue engineering uses autologous cell sources to overcome the immunogenic barriers of biomaterials.

PI3-Kinase-γ Has a Distinct and Essential Role in Lung-Specific Dendritic Cell Development.

Development of dendritic cells (DCs) commences in the bone marrow, from where pre-DCs migrate to peripheral organs to differentiate into mature DCs in situ. However, the factors that regulate organ-specific differentiation to give rise to tissue-specific DC subsets remain unclear. Here we show that the Ras-PI3Kγ-Akt-mTOR signaling axis acted downstream of FLT3L signaling and was required for development of lung CD103(+) DCs and, to a smaller extent, for lung CD11b(+) DCs, but not related DC populations in other non-lymphoid organs.

Specific and redundant roles of PKBα/AKT1 and PKBβ/AKT2 in human pancreatic islets.

Protein kinase Bα (PKBα)/AKT1 and PKBβ/AKT2 are required for normal peripheral insulin action but their role in pancreatic β cells remains enigmatic as indicated by the relatively mild islet phenotype of mice with deficiency for either one of these two isoforms. In this study we have analysed proliferation, apoptosis, β cell size and glucose-stimulated insulin secretion in human islets overexpressing either PKBα or PKBβ. Our results reveal redundant and specific functions.

Reduced hepatic lipid content in Pten-haplodeficient mice because of enhanced AKT2/PKBβ activation in skeletal muscle.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a major health problem and occurs frequently in the context of metabolic syndrome and type 2 diabetes mellitus. Hepatocyte-specific Pten-deficiency in mice was shown previously to result in hepatic steatosis due to hyperactivated AKT2. However, the role of peripheral insulin-sensitive tissues on PTEN- and AKT2-dependent accumulation of hepatic lipids has not been addressed.

Fibronectin coating of oxygenator membranes enhances endothelial cell attachment.

Background: Extracorporeal membrane oxygenation (ECMO) can replace the lungs' gas exchange capacity in refractory lung failure. However, its limited hemocompatibility, the activation of the coagulation and complement system as well as plasma leakage and protein deposition hamper mid- to long-term use and have constrained the development of an implantable lung assist device. In a tissue engineering approach, lining the blood contact surfaces of the ECMO device with endothelial cells might overcome these limitations.

Characterization and turnover of CD73/IP(3)R3-positive microvillar cells in the adult mouse olfactory epithelium.

The main olfactory epithelium consists of 4 major cell types: sensory neurons, supporting cells, microvillar cells, and basal progenitor cells. Several populations of microvillar olfactory cells have been described, whose properties are not yet fully understood. In this study, we aimed to clarify the classification of microvillar cells by introducing a specific marker, CD73.

Fibrin-based tissue engineering: comparison of different methods of autologous fibrinogen isolation.

Objective: This study is focussed on the optimal method of autologous fibrinogen isolation with regard to the yield and the use as a scaffold material. This is particularly relevant for pediatric patients with strictly limited volumes of blood.

Materials And Methods: The following isolation methods were evaluated: cryoprecipitation, ethanol (EtOH) precipitation, ammonium sulfate [(NH(4))(2)SO(4))] precipitation, ammonium sulfate precipitation combined with cryoprecipitation, and polyethylene glycol precipitation combined with cryoprecipitation.

Fibrin gel as alternative scaffold for respiratory tissue engineering.

Fibrin gel has proven a valuable scaffold for tissue engineering. Complex geometries can be produced by injection molding; it offers effective cell seeding and can be produced autologous. In order to evaluate its suitability for respiratory tissue engineering, we examined proliferation, functionality, and differentiation of respiratory epithelial cells on fibrin gel in comparison to culture on collagen-coated, microporous membranes.

Influence of platelet-derived growth factor-AB on tissue development in autologous platelet-rich plasma gels.

Fibrin-based scaffolds are widely used in tissue engineering. We postulated that the use of platelet-rich plasma (PRP) in contrast to platelet-poor plasma and pure fibrinogen as the basic material leads to an increased release of autologous platelet-derived growth factor (PDGF)-AB, which may have a consequent positive effect on tissue development. Therefore, we evaluated the release of PDGF-AB during the production process and the course of PDGF release during cultivation of plasma gels with and w/o platelets.

Tranexamic acid--an alternative to aprotinin in fibrin-based cardiovascular tissue engineering.

Recent clinical trials have led to the worldwide suspension of aprotinin, the most commonly used antifibrinolytic agent in fibrin-based tissue engineering. For future clinical applications of fibrin-based scaffolds, a suitable, alternative fibrinolysis inhibitor must be identified. The present study aimed to evaluate tranexamic acid (trans-4-aminomethyl-cyclohexane-1-carboxylic acid [t-AMCA]) as an alternative fibrinolysis inhibitor to aprotinin for cardiovascular tissue engineering applications.