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    Growth induction and low-oxygen apoptosis inhibition of human CD34 + progenitors in collagen gels
    (New York, NY : Hindawi, 2013) Avitabile, D.; Salchert, K.; Werner, C.; Capogrossi, M.C.; Pesce, M.
    Various reports have indicated low survival of injected progenitors into unfavorable environments such as the ischemic myocardium or lower limb tissues. This represents a major bottleneck in stem-cell-based cardiovascular regenerative medicine. Strategies to enhance survival of these cells in recipient tissues have been therefore sought to improve stem cell survival and ensure long-term engraftment. In the present contribution, we show that embedding human cord blood-derived CD34+ cells into a collagen I-based hydrogel containing cytokines is a suitable strategy to promote stem cell proliferation and protect these cells from anoxia-induced apoptosis.
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    Cytoskeletal transition in patterned cells correlates with interfacial energy model
    (London [u.a.] : Royal Society of Chemistry, 2014) Müller, A.; Meyer, J.; Paumer, T.; Pompe, T.
    A cell's morphology is intricately regulated by microenvironmental cues and intracellular feedback signals. Besides biochemical factors, cell fate can be influenced by the mechanics and geometry of the surrounding matrix. The latter point was addressed herein, by studying cell adhesion on two-dimensional micropatterns. Endothelial cells were grown on maleic acid copolymer surfaces structured with stripes of fibronectin by microcontact printing. Experiments showed a biphasic behaviour of actin stress fibre spacing in dependence on the stripe width with a critical size of approx. 15 μm. In a concurrent modelling effort, cells on stripes were simulated as droplet-like structures, including variations of interfacial energy, total volume and dimensions of the nucleus. A biphasic behaviour with regard to cell morphology and area was found, triggered by the minimum of interfacial energy, with the phase transition occurring at a critical stripe width close to the critical stripe width found in the cell experiment. The correlation of experiment and simulation suggests a possible mechanism of the cytoskeletal rearrangements based on interfacial energy arguments.
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    Glycosaminoglycan-based hydrogels to modulate heterocellular communication in in vitro angiogenesis models
    (London : Nature Publishing Group, 2014) Chwalek, K.; Tsurkan, M.V.; Freudenberg, U.; Werner, C.
    Angiogenesis, the outgrowth of blood vessels, is crucial in development, disease and regeneration. Studying angiogenesis in vitro remains challenging because the capillary morphogenesis of endothelial cells (ECs) is controlled by multiple exogenous signals. Therefore, a set of in situ-forming starPEG-heparin hydrogels was used to identify matrix parameters and cellular interactions that best support EC morphogenesis. We showed that a particular type of soft, matrix metalloproteinase-degradable hydrogel containing covalently bound integrin ligands and reversibly conjugated pro-angiogenic growth factors could boost the development of highly branched, interconnected, and lumenized endothelial capillary networks. Using these effective matrix conditions, 3D heterocellular interactions of ECs with different mural cells were demonstrated that enabled EC network modulation and maintenance of stable vascular capillaries over periods of about one month in vitro. The approach was also shown to permit in vitro tumor vascularization experiments with unprecedented levels of control over both ECs and tumor cells. In total, the introduced 3D hydrogel co-culture system could offer unique options for dissecting and adjusting biochemical, biophysical, and cell-cell triggers in tissue-related vascularization models.