Migration towards SDF-1 selects angiogenin-expressing bone marrow monocytes endowed with cardiac reparative activity in patients with previous myocardial infarction

INTRODUCTION: Chemokine-directed migration is crucial for homing of regenerative cells to the infarcted heart and correlates with outcomes of cell therapy trials. Hence, transplantation of chemokine-responsive bone marrow cells may be ideal for treatment of myocardial ischemia. To verify the therapeutic activity of bone marrow mononuclear cells (BM-MNCs) selected by in vitro migration towards the chemokine stromal cell-derived factor-1 (SDF-1) in a mouse model of myocardial infarction (MI), we used BM-MNCs from patients with previous large MI recruited in the TransACT-1&2 cell therapy trials. METHODS: Unfractioned BM-MNCs, SDF-1-responsive, and SDF-1-nonresponsive BM-MNCs isolated by patients recruited in the TransACT-1&2 cell therapy trials were tested in Matrigel assay to evaluate angiogenic potential. Secretome and antigenic profile were characterized by flow cytometry. Angiogenin expression was measured by RT-PCR. Cells groups were also intramyocardially injected in an in vivo model of MI (8-week-old immune deficient CD1-FOXN1(nu/nu) mice). Echocardiography and hemodynamic measurements were performed before and at 14 days post-MI. Arterioles and capillaries density, infiltration of inflammatory cells, interstitial fibrosis, and cardiomyocyte proliferation and apoptosis were assessed by immunohistochemistry. RESULTS: In vitro migration enriched for monocytes, while CD34(+) and CD133(+) cells and T lymphocytes remained mainly confined in the non-migrated fraction. Unfractioned total BM-MNCs promoted angiogenesis on Matrigel more efficiently than migrated or non-migrated cells. In mice with induced MI, intramyocardial injection of unfractionated or migrated BM-MNCs was more effective in preserving cardiac contractility and pressure indexes than vehicle or non-migrated BM-MNCs. Moreover, unfractioned BM-MNCs enhanced neovascularization, whereas the migrated fraction was unique in reducing the infarct size and interstitial fibrosis. In vitro studies on isolated cardiomyocytes suggest participation of angiogenin, a secreted ribonuclease that inhibits protein translation under stress conditions, in promotion of cardiomyocyte survival by migrated BM-MNCs. CONCLUSIONS: Transplantation of bone marrow cells helps post-MI healing through distinct actions on vascular cells and cardiomyocytes. In addition, the SDF-1-responsive fraction is enriched with angiogenin-expressing monocytes, which may improve cardiac recovery through activation of cardiomyocyte response to stress. Identification of factors linking migratory and therapeutic outcomes could help refine regenerative approaches. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-015-0028-y) contains supplementary material, which is available to authorized users

Defects activated photoluminescence in two-dimensional semiconductors: interplay between bound, charged, and free excitons

Point defects in semiconductors can trap free charge carriers and localize excitons. The interaction between these defects and charge carriers becomes stronger at reduced dimensionalities, and is expected to greatly influence physical properties of the hosting material. We investigated effects of anion vacancies in monolayer transition metal dichalcogenides as two-dimensional (2D) semiconductors where the vacancies density is controlled by alpha-particle irradiation or thermal-annealing. We found a new, sub-bandgap emission peak as well as increase in overall photoluminescence intensity as a result of the vacancy generation. Interestingly, these effects are absent when measured in vacuum. We conclude that in opposite to conventional wisdom, optical quality at room temperature cannot be used as criteria to assess crystal quality of the 2D semiconductors. Our results not only shed light on defect and exciton physics of 2D semiconductors, but also offer a new route toward tailoring optical properties of 2D semiconductors by defect engineering

Optical investigation of the natural electron doping in thin MoS2 films deposited on dielectric substrates

Two-dimensional (2D) compounds provide unique building blocks for novel layered devices and hybrid photonic structures. However, large surface-to-volume ratio in thin films enhances the significance of surface interactions and charging effects requiring new understanding. Here we use micro-photoluminescence (PL) and ultrasonic force microscopy to explore the influence of the dielectric environment on optical properties of a few monolayer MoS2 films. PL spectra for MoS2 films deposited on SiO2 substrates are found to vary widely. This film-to-film variation is suppressed by additional capping of MoS2 with SiO2 and SixNy, improving mechanical coupling of MoS2 with surrounding dielectrics. We show that the observed PL non-uniformities are related to strong variation in the local electron charging of MoS2 films. In completely encapsulated films, negative charging is enhanced leading to uniform optical properties. Observed great sensitivity of optical characteristics of 2D films to surface interactions has important implications for optoelectronics applications of layered materials

Mechanically controlled quantum interference in graphene break junctions

The ability to detect and distinguish quantum interference signatures is important for both fundamental research and for the realization of devices such as electron resonators1, interferometers2 and interference-based spin filters3. Consistent with the principles of subwavelength optics, the wave nature of electrons can give rise to various types of interference effects4, such as Fabry–Pérot resonances5, Fano resonances6 and the Aharonov–Bohm effect7. Quantum interference conductance oscillations8 have, indeed, been predicted for multiwall carbon nanotube shuttles and telescopes, and arise from atomic-scale displacements between the inner and outer tubes9,10. Previous theoretical work on graphene bilayers indicates that these systems may display similar interference features as a function of the relative position of the two sheets11,12. Experimental verification is, however, still lacking. Graphene nanoconstrictions represent an ideal model system to study quantum transport phenomena13–15 due to the electronic coherence16 and the transverse confinement of the carriers17. Here, we demonstrate the fabrication of bowtie-shaped nanoconstrictions with mechanically controlled break junctions made from a single layer of graphene. Their electrical conductance displays pronounced oscillations at room temperature, with amplitudes that modulate over an order of magnitude as a function of subnanometre displacements. Surprisingly, the oscillations exhibit a period larger than the graphene lattice constant. Charge-transport calculations show that the periodicity originates from a combination of the quantum interference and lattice commensuration effects of two graphene layers that slide across each other. Our results provide direct experimental observation of a Fabry–Pérot-like interference of electron waves that are partially reflected and/or transmitted at the edges of the graphene bilayer overlap region.Accepted Author ManuscriptQN/van der Zant LabBN/Cees Dekker La