A standardized procedure to obtain mesenchymal stem/stromal cells from minimally manipulated dental pulp and Wharton’s jelly samples

Transplantation of mesenchymal stem/stromal cells (MSCs) has emerged as an effective method to treat diseased or damaged organs and tissues, and hundreds of clinical trials using MSCs are currently under way to demonstrate the validity of such a therapeutic approach. However, most MSCs used for clinical trials are prepared in research laboratories with insufficient manufacturing quality control.In particular, laboratories lack standardized procedures for in vitro isolation of MSCs from tissue samples, resulting in heterogeneous populations of cells and variable experimental and clinical results. MSCs are now referred to as Human Cellular Tissue-based Products or Advanced Therapy Medicinal Products, and guidelines from the American Code of Federal Regulation of the Food and Drug Administration (21 CFR Part 1271) and from the European Medicines Agency (European Directive 1394/2007) define requirements for appropriate production of these cells. These guidelines, commonly called “Good Manufacturing Practices” (GMP), include recommendations about laboratory cell culture procedures to ensure optimal reproducibility, efficacy and safety of the final medicinal product. In particular, the Food and Drug Administration divides ex vivo cultured cells into “minimally” and “more than minimally” manipulated samples, in function of the use or not of procedures “that might alter the biological features of the cells”. Today, minimal manipulation conditions have not been defined for the collection and isolation of MSCs (Torre et al. 2015)(Ducret et al. 2015).Most if not all culture protocols that have been reported so far are unsatisfactory, because of the use of xeno- or allogeneic cell culture media, enzymatic treatment and long-term cell amplification that are known to alter the quality of MSCs. The aim of this study was to describe a standardized procedure for recovering MSCs with minimal handling from two promising sources, the dental pulp (DP) and the Wharton’s jelly (WJ) of the umbilical cord. The quality and homogeneity of the expanded cell populations were assessed by using flow cytometry with criteria that go beyond the International Society of Cellular Therapy (ISCT) guidelines for MSC characterization

Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts

BACKGROUND: This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. METHODS: Annual average particulate matter (PM10, PM2.5, PMabsorbance, PMcoarse), NO2, nitrogen oxides (NOx) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for ≥3 months of the year for ≥2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis. RESULTS: 15 279 and 10 537 participants respectively were included in the main NO2 and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO2 and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PMcoarse OR 1.31 (1.05 to 1.64) per 5 µg/m(3) increase and PM10 with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM2.5abs (black carbon) exposures. CONCLUSIONS: Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations

Measurement of residual nucleus cross sections and recoil energies in p + Fe collisions at 300, 500, 750, 1000 and 1500 MeV

The production of residual nuclei in p + Fe collisions has been measured at GSI on the FRS facility by means of the reverse kinematic techniques at 300, 500, 750, 1000 and 1500 MeV/A. The cross-sections larger than 0.01 mb of all isotopes with Z larger than 8 have been obtained. Velocity distributions were also measured. Comparisons to models describing spallation reactions and some empirical formulae often used in astrophysics are presented. These data are directly used to calculate impurety production and DPAs in a thin window as foreseen in spallation sources or accelerator-driven systems

Spallation Residues in the Reaction 56Fe + p at 0.3, 0.5, 0.75, 1.0 and 1.5 A GeV

The spallation residues produced in the bombardment of 56}Fe at 1.5, 1.0, 0.75, 0.5 and 0.3 A GeV on a liquid-hydrogen target have been measured using the reverse kinematics technique and the Fragment Separator at GSI (Darmstadt). This technique has permitted the full identification in charge and mass of all isotopes produced with cross-sections larger than 10^{-2} mb down to Z=8. Their individual production cross-sections and recoil velocities at the five energies are presented. Production cross-sections are compared to previously existing data and to empirical parametric formulas, often used in cosmic-ray astrophysics. The experimental data are also extensively compared to different combinations of intra-nuclear cascade and de-excitation models. It is shown that the yields of the lightest isotopes cannot be accounted for by standard evaporation models. The GEMINI model, which includes an asymmetric fission decay mode, gives an overall good agreement with the data. These experimental data can be directly used for the estimation of composition modifications and damages in materials containing iron in spallation sources. They are also useful for improving high precision cosmic-ray measurements.Comment: Submited to Phys. Rev. C (10/2006

Isospin dependent multifragmentation of relativistic projectiles

The N/Z dependence of projectile fragmentation at relativistic energies has been studied with the ALADIN forward spectrometer at the GSI Schwerionen Synchrotron (SIS). Stable and radioactive Sn and La beams with an incident energy of 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. For the interpretation of the data, calculations with the statistical multifragmentation model for a properly chosen ensemble of excited sources were performed. The parameters of the ensemble, representing the variety of excited spectator nuclei expected in a participant-spectator scenario, are determined empirically by searching for an optimum reproduction of the measured fragment-charge distributions and correlations. An overall very good agreement is obtained. The possible modification of the liquid-drop parameters of the fragment description in the hot freeze-out environment is studied, and a significant reduction of the symmetry-term coefficient is found necessary to reproduce the mean neutron-to-proton ratios /Z and the isoscaling parameters of Z<=10 fragments. The calculations are, furthermore, used to address open questions regarding the modification of the surface-term coefficient at freeze-out, the N/Z dependence of the nuclear caloric curve, and the isotopic evolution of the spectator system between its formation during the initial cascade stage of the reaction and its subsequent breakup.Comment: 23 pages, 29 figures, published in Physical Review

The first determination of Generalized Polarizabilities of the proton by a Virtual Compton Scattering experiment

Absolute differential cross sections for the reaction (e+p -> e+p+gamma) have been measured at a four-momentum transfer with virtuality Q^2=0.33 GeV^2 and polarization \epsilon = 0.62 in the range 33.6 to 111.5 MeV/c for the momentum of the outgoing photon in the photon-proton center of mass frame. The experiment has been performed with the high resolution spectrometers at the Mainz Microtron MAMI. From the photon angular distributions, two structure functions which are a linear combination of the generalized polarizabilities have been determined for the first time.Comment: 4 pages, 3 figure

Isotopic Dependence of the Nuclear Caloric Curve

The A/Z dependence of projectile fragmentation at relativistic energies has been studied with the ALADIN forward spectrometer at SIS. A stable beam of 124Sn and radioactive beams of 124La and 107Sn at 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. Chemical freeze-out temperatures are found to be nearly invariant with respect to the A/Z of the produced spectator sources, consistent with predictions for expanded systems. Small Coulomb effects (\Delta T \approx 0.6 MeV) appear for residue production near the onset of multifragmentation.Comment: 11 pages, 3 figures, accepted for publ. in Phys. Rev. Let