In the human body, secreted growth factors and cytokines instruct, among others, proliferation, differentiation, and migration. In the hematopoietic stem cell (HSC) niche, stromal cells provide instructive cues to stem cells via paracrine signaling and one of these cell types, known to secrete a broad panel of growth factors and cytokines, is mesenchymal stromal cells (MSCs). The factors secreted by MSCs have trophic, immunomodulatory, antiapoptotic, and proangiogenic properties, and their paracrine profile varies according to their initial activation by various stimuli. MSCs are currently studied as treatment for

inflammatory diseases such as graft-versus-host disease and Crohn’s disease, but also as treatment for myocardial infarct and solid organ transplantation. In addition, MSCs are investigated for their use in tissue engineering applications, in which their differentiation plays KPT-8602 an important role, but as we have recently demonstrated, their trophic factors BMS-777607 may also be involved. Furthermore, a functional improvement of MSCs might be obtained after preconditioning or tailoring the cells themselves. Also, the way the cells are clinically administered may be specialized for specific therapeutic scenarios. In this review we will first discuss the HSC niche, in which MSCs were recently identified and are thought to play an instructive and

supportive role. We will then evaluate therapeutic applications that currently try to utilize the trophic and/or immunomodulatory properties of MSCs, and we will also discuss new options to enhance their therapeutic

effects.”
“Epitaxial nanotwinned Cu films, with an average twin spacing ranging from 7 to 16 nm, exhibit a high ratio of strength-to-electrical resistivity, similar to 400 MPa (mu Omega cm)(-1). The hardness of these Cu films approaches 2.8 GPa, and their electrical resistivities are comparable to that of oxygen-free high-conductivity Cu. Compared to high-angle grain boundaries, coherent twin interfaces possess inherently high resistance to the transmission of single dislocations, and yet an order of magnitude lower electron scattering coefficient, determined to be 1.5-5 X 10(-7) mu Omega cm(2) at room temperature. Analytical PP2 studies as well as experimental results show that, in polycrystalline Cu, grain refinement leads to a maximum of the strength-to-resistivity ratio, similar to 250 MPa (mu Omega cm)(-1), when grain size is comparable to the mean-free path of electrons. However, in twinned Cu, such a ratio increases continuously with decreasing twin spacing down to a few nanometers. Hence nanoscale growth twins are more effective to achieve a higher strength-to-resistivity ratio than high-angle grain boundaries. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.