Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that leads to severe neurological deficits. Due to their immunomodulatory and neuroprotective activities and their ability to promote the generation of oligodendrocytes, mesenchymal stem cells (MSCs) are currently being developed for autologous cell therapy in MS. As aging reduces the regenerative capacity of all tissues, it is of relevance to investigate whether MSCs retain their pro-oligodendrogenic activity with increasing age. We demonstrate that MSCs derived from aged rats have a reduced capacity to induce oligodendrocyte differentiation of adult CNS stem/progenitor cells. Aging also abolished the ability of MSCs to enhance the generation of myelin-like sheaths in demyelinated cerebellar slice cultures. Finally, in a rat model for CNS demyelination, aging suppressed the capability of systemically transplanted MSCs to boost oligodendrocyte progenitor cell (OPC) differentiation during remyelination. Thus, aging restricts the ability of MSCs to support the generation of oligodendrocytes and consequently inhibits their capacity to enhance the generation of myelin-like sheaths. These findings may impact on the design of therapies using autologous MSCs in older MS patients.The authors would like to thank the following funding agencies for their support: Paracelsus Medical University PMU-FFF Long-Term Fellowship L-12/01/001-RIV (to and Stand-Alone Grant E-12/15/077-RIT (both to F.J.R.); Chilean Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) FONDECYT Program Regular Grant Nº 1161787 (to F.J.R.), Regular Grant Nº 1141015 (to L.F.B.); Chilean CONICYT PCI Program Grant Nº REDES170233 (to F.J.R.), Grant Nº REDES180139 and Grant Nº REDI170037; Chilean CONICYT FONDEFIDeA Program Grant Nº ID17AM0043 (to M.E.S. and F.J.R.); European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements N HEALTH-F2-2011-278850 (INMiND) and HEALTH-F2-2011-279288 (IDEA). The work in the Küry laboratory was supported by the German Research Foundation (DFG; KU1934/2_1, KU1934/5-1) and the Christiane and Claudia Hempel Foundation for clinical and iBrain. The work in the Franklin laboratory was supported by grants from the UK Multiple Sclerosis Society and the Adelson Medical Research Foundation, and a core support grant from the Wellcome Trust and MRC to the Wellcome-MRC Cambridge Stem Cell Institute. In addition, the present work was supported by the state of Salzburg (to L.A.). We thank Armin Schneider, Sygnis Pharma AG Heidelberg, Germany, for the MBP promoter construct. We disclose any conflict of interest

Simple Metals at High Pressure

In this lecture we review high-pressure phase transition sequences exhibited by simple elements, looking at the examples of the main group I, II, IV, V, and VI elements. General trends are established by analyzing the changes in coordination number on compression. Experimentally found phase transitions and crystal structures are discussed with a brief description of the present theoretical picture.Comment: 22 pages, 4 figures, lecture notes for the lecture given at the Erice course on High-Pressure Crystallography in June 2009, Sicily, Ital

Understanding Novel Superconductors with Ab Initio Calculations

This chapter gives an overview of the progress in the field of computational superconductivity. Following the MgB2 discovery (2001), there has been an impressive acceleration in the development of methods based on Density Functional Theory to compute the critical temperature and other physical properties of actual superconductors from first-principles. State-of-the-art ab-initio methods have reached predictive accuracy for conventional (phonon-mediated) superconductors, and substantial progress is being made also for unconventional superconductors. The aim of this chapter is to give an overview of the existing computational methods for superconductivity, and present selected examples of material discoveries that exemplify the main advancements.Comment: 38 pages, 10 figures, Contribution to Springer Handbook of Materials Modellin