Toll-like receptor 2/6-dependent stimulation of mesenchymal stem cells promotes angiogenesis by paracrine factors

Reconstruction of critical size bone defects represents a major challenge in orthopaedic surgery. Insufficient angiogenesis is a limiting factor for engraftment of large-scale tissue transplants. Transplantation or stimulation of local mesenchymal stem cells (MSCs) represents a potential solution to enhance angiogenesis. We recently identified angiogenic properties for the Toll-like receptor (TLR) 2/6 agonist MALP-2 and now investigated if MALP-2 could be used to stimulate MSCs in order to promote angiogenesis in vitro and in vivo.Human MSCs from the bone marrow of healthy subjects were isolated, cultured and expanded in vitro and were shown to be positive for mesenchymal stem cells markers as well as for the MALP-2 receptors TLR2 and TLR6. MALP-2 directly enhanced migration but not proliferation of human MSCs. Conditioned medium from MALP-2 stimulated MSCs significantly increased proliferation, migration and tube formation of endothelial cells. Analysis of the conditioned medium from MSCs revealed that MALP-2 stimulation enhanced the secretion of several chemokines and growth factors including vascular endothelial growth factors (VEGF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Finally, we studied MALP-2 effects on MSCs in a sheep model of tissue engineering in vivo. Therefore, MSCs were isolated from the iliac crest of black head sheep and co-cultivated with MALP-2 ex vivo. Implantation of autologous MSCs within a scaffold cylinder into the M. latissimus dorsi significantly enhanced vessel density of these constructs after 6 months.We here present the first evidence that TLR2/6-dependent stimulation of MSCs promotes angiogenesis in vitro and in vivo offering a novel strategy for therapeutic angiogenesis, e.g., for tissue engineering of bone

IFT88 transports Gucy2d, a guanylyl cyclase, to maintain sensory cilia function in Drosophila

Cilia are involved in a plethora of motility and sensory-related functions. Ciliary defects cause several ciliopathies, some of which with late-onset, suggesting cilia are actively maintained. While much is known about cilia assembly, little is understood about the mechanisms of their maintenance. Given that intraflagellar transport (IFT) is essential for cilium assembly, we investigated the role of one of its main players, IFT88, in ciliary maintenance. We show that DmIFT88, the Drosophila melanogaster orthologue of IFT88, continues to move along fully formed sensory cilia, and that its acute knockdown in the ciliated neurons of the adult affects sensory behaviour. We further identify DmGucy2d, the Drosophila guanylyl cyclase 2d, as a DmIFT88 cargo, whose loss also leads to defects in sensory behaviour maintenance. DmIFT88 binds to the intracellular part of DmGucy2d, a highly, evolutionarily conserved and mutated in several degenerative retina diseases, taking the cyclase into the cilia. Our results offer a novel mechanism for the maintenance of sensory cilia function and its potential role in human diseases

Hard Tissue Engineering

Peer reviewe

Insect Bio-inspired Neural Network Provides New Evidence on How Simple Feature Detectors Can Enable Complex Visual Generalization and Stimulus Location Invariance in the Miniature Brain of Honeybees

This work was supported by a Human Frontier Science Program Grant RGP0022/2014 to LC and Queen Mary University of London Scholarship to MR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Sensing pH with TMCs

Transmembrane channel-like (TMC) proteins have been implicated in hair cell mechanotransduction, Drosophila proprioception, and sodium sensing in the nematode C. elegans. In this issue of Neuron, Wang et al. (2016) report that C. elegans TMC-1 mediates nociceptor responses to high pH, not sodium, allowing the nematode to avoid strongly alkaline environments in which most animals cannot survive

A modular approach for co-simulations of integrated multi-energy systems: Coupling multi-energy grids in existing environments of grid planning & operation tools

Renewable energy sources are already the profound deliverers of electrical energy in Germany, while the problem to manage the gap between volatile prosumers and mostly user-dependent consumers are still not solved. One approach to overcome this challenge is the use of the given infrastructure of gas and district heating systems acting as buffer. However, not talking about simulating integrated multi-energy systems, especially the embedment of these in already existing systems is going to be a massive challenge in the future. In this paper, we introduce a way how systems widely used in different energy sectors can be combined and managed together. The approach follows a modular concept easily connecting well-known systems with new algorithms and model extensions. This shall be exemplified shown by creating an integrated multi-energy system consisting of an electrical and gas grid both modelled in PSS ® Sincal distributed by SIEMENS

SimBench: Open source time series of power load, storage and generation for the simulation of electrical distribution grids

In operation and planning of electrical grids, it is essential to account for temporal fluctuation of produced and consumed electric energy. Time series based studies often use standardized load profiles for this, which, however, cannot accurately represent the individual peak patterns in load and demand and their random combinations. As part of the SimBench project, we developed a dataset of energy time series to be assigned as individual profiles to grid nodes in high voltage (HV), medium voltage (MV) and low voltage (LV) grids to calculate local power flows in a more realistic way. Load profiles are classified and assigned to categories on the basis of similarity to standard load profiles to represent a broad range of energy users and generation profiles were created using weather data and an agent-based simulation tool. The subset presented in this paper comprises different 77 one-year-profiles with a 15 minute resolution, containing commercial consumers, household consumers, storage, and production units based on real measurements from Germany with a focus on MV and LV levels

Berücksichtigung lokaler und sektorübergreifender Einflussgrößen bei der Planung städtischer Verteilnetze: Paper präsentiert auf der Tagung Zukünftige Stromnetze für Erneuerbare Energien 2018; 30. und 31. Januar 2018, Steigenberger Hotel am Kanzleramt Berlin

Im städtischen Kontext werden häufig Mehrspartenenergiesysteme, bestehend aus einer Gas-, Wärme- und Strominfrastruktur betrieben. In Zukunft ist bedingt durch die Wärmewende mit einer Teilelektrifizierung des Wärmesektors zu rechnen, wobei Wärmeerzeugungsanlagen überwiegend in das Niederspannungsnetz eindringen. Für die Szenarioerstellung werden Modelle nötig, mit denen die Versorgungsaufgabe lokal, bedarfsorientiert und unter Berücksichtigung der bestehenden Netzinfrastrukturen definiert werden kann. Mit der vorgestellten Methodik wird ein komplett georeferenziertes Gebäudemodell aller Wohngebäude im Versorgungsgebiet der Stadtwerke Bamberg (81.661 Einwohner) erstellt, auf dessen Basis die Berechnung bzw. Approximation des spez. Heizwärmebedarfes aller Liegenschaften, sowie der Entwurf eines Szenarios für den Zubau el. Wärmeerzeugungsanlagen erfolgt. Dieses bildet die Grundlage zur Beurteilung des Einflusses el. Heizanlagen auf das Mittel- und Niederspannungsnetz des Versorgungsgebietes „Bamberg Ost“. Dazu wird der aktuelle und zukünftige Netzzustand in Form von Worst-Case-Analysen berechnet