Organotypic heart slices represent a multicellular model of the human myocardium and a novel platform for studies ranging from the investigation of molecular interactions to tissue engineering.

ObjectiveA network of endogenous circadian clocks adapts physiology and behavior to recurring changes in environmental demands across the 24-hour day cycle. Circadian disruption promotes weight gain and type 2 diabetes development. In this study, we aim to dissect the roles of different tissue clocks in the regulation of energy metabolism.MethodsWe used mice with genetically ablated clock function in the circadian pacemaker of the suprachiasmatic nucleus (SCN) under different light and feeding conditions to study peripheral clock resetting and the role of the peripheral clock network in the regulation of glucose handling and metabolic homeostasis.ResultsIn SCN clock-deficient mice, behavioral and non-SCN tissue clock rhythms are sustained under rhythmic lighting conditions but deteriorate quickly in constant darkness. In parallel to the loss of behavioral and molecular rhythms, the animals develop adiposity and impaired glucose utilization in constant darkness. Restoring peripheral clock rhythmicity and synchrony by time-restricted feeding normalizes body weight and glucose metabolism.ConclusionsThese data reveal the importance of an overall synchronized circadian clockwork for the maintenance of metabolic homeostasis.

Human skin harbours multiple different stem cell populations. In contrast to the relatively well-characterized niches of epidermal and hair follicle stem cells, the localization and niches of stem cells in other human skin compartments are as yet insufficiently investigated. Previously, we had shown in a pilot study that human sweat gland stroma contains Nestin-positive stem cells. Isolated sweat gland stroma-derived stem cells (SGSCs) proliferated in vitro and expressed Nestin in 80% of the cells. In this study, we were able to determine the precise localization of Nestin-positive cells in both eccrine and apocrine sweat glands of human axillary skin. We established a reproducible isolation procedure and characterized the spontaneous, long-lasting multipotent differentiation capacity of SGSCs. Thereby, a pronounced ectodermal differentiation was observed. Moreover, the secretion of prominent cytokines demonstrated the immunological potential of SGSCs. The comparison to human adult epidermal stem cells (EpiSCs) and bone marrow stem cells (BMSCs) revealed differences in protein expression and differentiation capacity. Furthermore, we found a coexpression of the stem cell markers Nestin and Iα6 within SGSCs and human sweat gland stroma. In conclusion the initial results of the pilot study were confirmed, indicating that human sweat glands are a new source of unique stem cells with multilineage differentiation potential, high proliferation capacity and remarkable self renewal. With regard to the easy accessibility of skin tissue biopsies, an autologous application of SGSCs in clinical therapies appears promising.

Toward a new generation of improved nerve guidance conduits (NGCs), novel biomaterials are required to address pressing clinical shortcomings in peripheral nerve regeneration (PNR) and to promote biological performance. A dual-component hydrogel system formed by cross-linking reaction between maleic anhydride groups in an oligomeric building block for cross-linking of free amine functionalities in partially hydrolyzed collagen is formulated for continuous processing and NGC fabrication. The influence of the gelation base is optimized for processing from a double syringe delivery system with a static mixer. A hydrophilic low-concentrated base was introduced to control network formation and to utilize highly reactive macromers for gelation. Cross-linking extent and building block conversion were improved and homogenous monoliths were fabricated. Chemically derivatized hydrogels were obtained by conversion of a fraction of anhydride groups in the oligomeric precursor with monovalent primary amine-containing grafting molecules prior to gelation. Network stability in functionalized hydrogels was maintained and cationic moieties were implement to the gel that promoted in vitro cell attachment and spreading irrespective of mechanical stiffness. A molding strategy was introduced that allowed for fabrication of flexible tubular conduits in tunable dimensions and with chemically patterned structures. These hydrogel-based conduits hold promise for the next generation NGCs with integrated chemical cues for PNR.

No abstract