Human mesenchymal stromal cells : biological characterization and clinical application

This thesis focuses on the characterization of the biological and functional properties of human mesenchymal stromal cells (MSCs), isolated from different tissue sources. The differentiation capacity of MSCs from fetal and adult tissues has been tested and compared. Umbilical cord blood (UCB) has been investigated as a potential novel source of MSCs for clinical application and the immunomodulatory properties of UCB-derived MSCs have been characterized in comparison with those of MSCs of bone marrow (BM) origin. Moreover, it has been attempted to optimize the experimental conditions for MSC ex vivo expansion. Alternative culture methods, devoid of animal proteins, have been applied by introducing expansion procedures based on platelet-derived growth factors. The potential susceptibility of MSCs to undergo malignant transformation after long-term in vitro culture has been investigated and discussed in view of their clinical application, especially in immunocompromised hosts. The role of MSC therapy in the context of hematopoietic stem cell transplantation (HSCT) has been explored, focusing in particular on the co-transplantation of MSCs to promote engraftment of hematopoietic progenitors, and on the administration of MSCs for the treatment of steroid-resistant, severe acute graft-versus-host disease (GvHD). The role of MSCs in the treatment of inflammatory bowel diseases refractory to conventional therapies, as well as the concept for treating refractory autoimmune diseases has been discussed.UBL - phd migration 201

Effect of 15 BMI-Associated polymorphisms, reported for europeans, across ethnicities and degrees of amerindian ancestry in mexican children

In Mexico, the genetic mechanisms underlying childhood obesity are poorly known. We evaluated the effect of loci, known to be associated with childhood body mass index (BMI) in Europeans, in Mexican children from different ethnic groups. We performed linear and logistic analyses of BMI and obesity, respectively, in Mestizos and Amerindians (Seris, Yaquis and Nahuatl speakers) from Northern (n = 369) and Central Mexico (n = 8545). We used linear models to understand the effect of degree of Amerindian ancestry (AMA) and genetic risk score (GRS) on BMI z-score. Northern Mexican Mestizos showed the highest overweight-obesity prevalence (47.4%), followed by Seri (36.2%) and Central Mexican (31.5%) children. Eleven loci (SEC16B/rs543874, OLFM4/rs12429545/rs9568856, FTO/rs9939609, MC4R/rs6567160, GNPDA2/rs13130484, FAIM2/rs7132908, FAM120AOS/rs944990, LMX1B/rs3829849, ADAM23/rs13387838, HOXB5/rs9299) were associated with BMI and seven (SEC16B/rs543874, OLFM4/rs12429545/rs9568856, FTO/rs9939609, MC4R/rs6567160, GNPDA2 rs13130484, LMX1B/rs3829849) were associated with obesity in Central Mexican children. One SNP was associated with obesity in Northern Mexicans and Yaquis (SEC16B/rs543874). We found higher BMI z-score at higher GRS (β = 0.11, p = 0.2 × 10−16) and at lower AMA (β = −0.05, p = 6.8 × 10−7). The GRS interacts with AMA to increase BMI (β = 0.03, p = 6.08 × 10−3). High genetic BMI susceptibility increase the risk of higher BMI, including in Amerindian children

Genomic Deletion Marking an Emerging Subclone of Francisella tularensis subsp. holarctica in France and the Iberian Peninsula

P. 7465-7470Francisella tularensis subsp. holarctica is widely disseminated in North America and the boreal and temperate regions of the Eurasian continent. Comparative genomic analyses identified a 1.59-kb genomic deletion specific to F. tularensis subsp. holarctica isolates from Spain and France. Phylogenetic analysis of strains carrying this deletion by multiple-locus variable-number tandem repeat analysis showed that the strains comprise a highly related set of genotypes, implying that these strains were recently introduced or recently emerged by clonal expansion in France and the Iberian PeninsulaS

Mesenchymal stem/stromal cells: a new ''cells as drugs'' paradigm : efficacy and critical aspects in cell therapy

Mesenchymal stem cells (MSCs) were first isolated more than 50 years ago from the bone marrow. Currently MSCs may also be isolated from several alternative sources and they have been used in more than a hundred clinical trials worldwide to treat a wide variety of diseases. The MSCs mechanism of action is undefined and currently under investigation. For in vivo purposes MSCs must be produced in compliance with good manufacturing practices and this has stimulated research on MSCs characterization and safety. The objective of this review is to describe recent developments regarding MSCs properties, physiological effects, delivery, clinical applications and possible side effects

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)