c-Fos induces chondrogenic tumor formation in immortalized human mesenchymal progenitor cells

Mesenchymal progenitor cells (MPCs) have been hypothesized as cells of origin for sarcomas, and c-Fos transcription factor has been showed to act as an oncogene in bone tumors. In this study, we show c-Fos is present in most sarcomas with chondral phenotype, while multiple other genes are related to c-Fos expression pattern. To further define the role of c-Fos in sarcomagenesis, we expressed it in primary human MPCs (hMPCs), immortalized hMPCs and transformed murine MPCs (mMPCs). In immortalized hMPCs, c-Fos expression generated morphological changes, reduced mobility capacity and impaired adipogenic- and osteogenic-differentiation potentials. Remarkably, immortalized hMPCs or mMPCs expressing c-Fos generated tumors harboring a chondrogenic phenotype and morphology. Thus, here we show that c-Fos protein has a key role in sarcomas and that c-Fos expression in immortalized MPCs yields cell transformation and chondrogenic tumor formation

In Vivo Ectopic Implantation Model to Assess Human Mesenchymal Progenitor Cell Potential

Clinical interest on human mesenchymal progenitor cells (hMPC) relies on their potential applicability in cell-based therapies. An in vitro characterization is usually performed in order to define MPC potency. However, in vitro predictions not always correlate with in vivo results and thus there is no consensus in how to really assess cell potency. Our goal was to provide an in vivo testing method to define cell behavior before therapeutic usage, especially for bone tissue engineering applications. In this context, we wondered whether bone marrow stromal cells (hBMSC) would proceed in an osteogenic microenvironment. Based on previous approaches, we developed a fibrin/ceramic/BMP-2/hBMSCs compound. We implanted the compound during only 2 weeks in NOD-SCID mice, either orthotopically to assess its osteoinductive property or subcutaneously to analyze its adequacy as a cell potency testing method. Using fluorescent cell labeling and immunohistochemistry techniques, we could ascertain cell differentiation to bone, bone marrow, cartilage, adipocyte and fibrous tissue. We observed differences in cell potential among different batches of hBMSCs, which did not strictly correlate with in vitro analyses. Our data indicate that the method we have developed is reliable, rapid and reproducible to define cell potency, and may be useful for testing cells destined to bone tissue engineering purposes. Additionally, results obtained with hMPCs from other sources indicate that our method is suitable for testing any potentially implantable mesenchymal cell. Finally, we propose that this model could successfully be employed for bone marrow niche and bone tumor studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12015-013-9464-1) contains supplementary material, which is available to authorized users

Comparative study of different discrete element models and evaluation of equivalent micromechanical parameters

AbstractComparative studies of different discrete element models of a rock-type material are presented. The discrete element formulation employs spherical particles with the cohesive interaction model combining linear elastic behaviour with brittle failure. Numerical studies consisted in simulation of the uniaxial compression test. Two cylindrical specimens with particle size distributions yielding different degree of heterogeneity have been used. Macroscopic response produced by different discrete element models has been compared. The main difference between the compared models consists in the evaluation of micromechanical constitutive parameters. Two approaches are compared. In the first approach, the contact stiffness and strength parameters depend on the local particle size, while in the second approach, global uniform contact parameters are assumed for all the contacting pairs in function of average geometric measures characterizing the particle assembly. The size dependent contact parameters are calculated as functions of geometric parameters characterizing each contacting particle pair. As geometric scaling parameters, the arithmetic and harmonic means, as well as the minimum of the radii of two contacting particles are considered. Two different models with size dependent contact parameters are formulated. The performance of these models is compared with that of the discrete element model with global uniform contact parameters. Equivalence between the models with size dependent and uniform contact parameters has been checked. In search of this equivalence, different methods of evaluation of global uniform parameters have been studied. The contact stiffness has been evaluated in terms of the average radius of the particle assembly or in terms of the averages of the arithmetic and harmonic means of the contact pair radii, the geometric parameters used in the evaluation of the contact stiffness in the size-dependent models. The uniform contact strengths have been determined as functions of the averages of radii squares, squares of arithmetic radii means or squares of minimum radii of the contacting pairs.For the more homogenous specimen, the models with local size dependent parameters and models with global uniform parameters give similar response. The models with uniform parameters evaluated according to the averages of the geometric parameters used in the evaluation of local parameters ensure better agreement with the respective models with size-dependent parameters than the models with uniform parameters evaluated according to the particle radii. Simulations using the more heterogenous specimen reveal differences between the considered models. There are significant differences in stress–strain curves as well as in the failure pattern. The models with local size-dependent parameters are more sensitive to the change of heterogeneity than the model with global uniform parameters

Genomic Epidemiology of 2015-2016 Zika Virus Outbreak in Cape Verde

During 2015-2016, Cape Verde, an island nation off the coast of West Africa, experienced a Zika virus (ZIKV) outbreak involving 7,580 suspected Zika cases and 18 microcephaly cases. Analysis of the complete genomes of 3 ZIKV isolates from the outbreak indicated the strain was of the Asian (not African) lineage. The Cape Verde ZIKV sequences formed a distinct monophylogenetic group and possessed 1-2 (T659A, I756V) unique amino acid changes in the envelope protein. Phylogeographic and serologic evidence support earlier introduction of this lineage into Cape Verde, possibly from northeast Brazil, between June 2014 and August 2015, suggesting cryptic circulation of the virus before the initial wave of cases were detected in October 2015. These findings underscore the utility of genomic-scale epidemiology for outbreak investigations.status: publishe

Genomic Epidemiology of 2015–2016 Zika Virus Outbreak in Cape Verde

International audienceDuring 2015-2016, Cape Verde, an island nation off the coast of West Africa, experienced a Zika virus (ZIKV) outbreak involving 7,580 suspected Zika cases and 18 microcephaly cases. Analysis of the complete genomes of 3 ZIKV isolates from the outbreak indicated the strain was of the Asian (not African) lineage. The Cape Verde ZIKV sequences formed a distinct monophylogenetic group and possessed 1-2 (T659A, I756V) unique amino acid changes in the envelope protein. Phylogeographic and serologic evidence support earlier introduction of this lineage into Cape Verde, possibly from northeast Brazil, between June 2014 and August 2015, suggesting cryptic circulation of the virus before the initial wave of cases were detected in October 2015. These findings underscore the utility of genomic-scale epidemiology for outbreak investigations