Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: a preliminary study on biglycan-deficient murine model of chronic disc degeneration

INTRODUCTION: Biglycan is an important proteoglycan of the extracellular matrix of intervertebral disc (IVD), and its decrease with aging has been correlated with IVD degeneration. Biglycan deficient (Bgn(−/0)) mice lack this protein and undergo spontaneous IVD degeneration with aging, thus representing a valuable in vivo model for preliminary studies on therapies for human progressive IVD degeneration. The purpose of the present study was to assess the possible beneficial effects of adipose-derived stromal cells (ADSCs) implants in the Bgn(−/0) mouse model. METHODS: To evaluate ADSC implant efficacy, Bgn(−/0) mice were intradiscally (L1-L2) injected with 8x10(4) ADSCs at 16 months old, when mice exhibit severe and complete IVD degeneration, evident on both 7Tesla Magnetic Resonance Imaging (7TMRI) and histology. Placebo and ADSCs treated Bgn(−/0) mice were assessed by 7TMRI analysis up to 12 weeks post-transplantation. Mice were then sacrificed and implanted discs were analyzed by histology and immunohistochemistry for the presence of human cells and for the expression of biglycan and aggrecan in the IVD area. RESULTS: After in vivo treatment, 7TMRI revealed evident increase in signal intensity within the discs of mice that received ADSCs, while placebo treatment did not show any variation. Ultrastructural analyses demonstrated that human ADSC survival occurred in the injected discs up to 12 weeks after implant. These cells acquired a positive expression for biglycan, and this proteoglycan was specifically localized in human cells. Moreover, ADSC treatment resulted in a significant increase of aggrecan tissue levels. CONCLUSION: Overall, this work demonstrates that ADSC implant into degenerated disc of Bgn(−/0) mice ameliorates disc damage, promotes new expression of biglycan and increased levels of aggrecan. This suggests a potential benefit of ADSC implant in the treatment of chronic degenerative disc disease and prompts further studies in this field

Superparamagnetic Nanoparticles as High Efficiency Magnetic Resonance Imaging T-2 Contrast Agent

Nanoparticle-based magnetic resonance imaging T-2 negative agents are of great interest, and much effort is devoted to increasing cell loading capability while maintaining low cytotoxicity. Herein, two classes of mixed-ligand protected magnetic-responsive, bimetallic gold/iron nano particles (Au/Fe NPs) synthesized by a two-step method are presented. Their structure, surface composition, and magnetic properties are characterized. The two classes of sulfonated Au/Fe NPs, with an average diameter of 4 nm, have an average atomic ratio of Au to Fe equal to 7 or 8, which enables the Au/Fe NPs to be superparamagnetic with a blocking temperature of 56 K and 96 K. Furthermore, preliminary cellular studies reveal that both Au/Fe NPs show very limited toxicity. MRI phantom experiments show that r(2)/r(1) ratio of Au/Fe NPs is as high as 670, leading to a 66% reduction in T-2 relaxation time. These nanoparticles provide great versatility and potential for nanopartide-based diagnostics and therapeutic applications and as imaging contrast agents

Superconducting fluctuating diamagnetism versus precursor diamagnetism in heterogeneous superconductors

The fluctuation-induced diamagnetism (FD) above the transition temperature T, is studied through the isothermal field-dependence of the diamagnetic magnetization M-d iota a. While for T approximate to T-c and H -> 0 one has-M-d iota a proportional to (H)(1/2),on increasing field an upturn occurs and vertical bar M-dia vertical bar begins to decrease, in correspondence to field-induced quenching of the fluctuating pairs. For BCS superconductors (SC) as MgB2 the upturn field H-up is in the range 100-800 Oe, while in optimally doped high-temperature SC(HTcSC) Hup is expected in the range of several Tesla, because of the small coherence length. At variance, in non-homogeneous HTcSC (under- or overdoped) or in the presence of impurities causing diffuse transition, strong increase Of M-d iota a and Hup reduced by order of magnitudes are observed. The reasons of these behaviors are discussed in the report. In particular the difference between the FD in heterogeneous HTcSC (related to SF) and the precursor diamagnetism for diffuse transitions such as in Al-doped MgB2 (unrelated to SF) is emphasized and it is shown how the temperature dependence of H-up discriminates between the two effects

Assessment of human hippocampal developmental neuroanatomy by means of ex-vivo 7 T magnetic resonance imaging

During development, the hippocampus undergoes numerous changes in its cell morphology and cyto- and myelo-architecture that begin during the fetal period and continue after birth. We investigated the developmental changes occurring in healthy fetal (20-32 gestational weeks) and post-natal human hippocampi (from 1 day to adulthood) by combining high-resolution 7 T magnetic resonance imaging (MRI) and histological and immunohistochemical analyses in order to compare variations in signal intensity with cyto- and myeloarchitectural organization. During fetal period the intensity of the T2-weighted images was related to the cell density and the subregions of Ammon's horn and dentate gyrus, characterized by densely packed neurons, were recognizable as hypointense areas. The inverse correlation between MRI signal intensity and cell density was visualized by line profile results. At the age of two post-natal weeks, the low MRI signal was still related to cell density, although thin myelinated fibers were observed in hypointense regions such as the alveus and stratum lacunosum-moleculare. The myelin content subsequently increases until the complete hippocampal myeloarchitecture is reached in adulthood. Comparison of the MRI findings and corresponding histological sections indicated that the differences in the T2-weighted images between the age of seven years and adulthood reflect the increasing density of myelinated fibers. These results provide useful information concerning the interpretation of MRI signals and the developmental changes visualized by in vivo MRI at lower field strengths, and may be used as a reference for the future use of high spatial resolution MRI in clinical practic

Anomaly in YBa2Cu4O8 charge distribution below T-c: A zero-field muon spin relaxation study

Zero-field muon spin-relaxation µSR measurements in 63Cu isotope enriched and natural YBa2Cu4O8 powders are presented. The µ+ relaxation rate is characterized by a sizeable enhancement as the temperature is lowered below the superconducting transition temperature Tc. The comparison of the asymmetry decay in the two samples reveals that the µ+ relaxation is driven by nuclear dipole interaction from 300 K down to 4.2 K. It is argued that the increase in the relaxation rate below Tc originates from a change either of the µ+ site or of the orientation of the electric-field gradient at the Cu nuclei, due to a modification in the charge distribution within CuO chains