iPSCs-based generation of vascular cells: reprogramming approaches and applications

Recent advances in the field of induced pluripotent stem cells (iPSCs) research have opened a new avenue for stem cell-based generation of vascular cells. Based on their growth and differentiation potential, human iPSCs constitute a well-characterized, generally unlimited cell source for the mass generation of lineage- and patient-specific vascular cells without any ethical concerns. Human iPSCs-derived vascular cells are perfectly suited for vascular disease modeling studies because patient-derived iPSCs possess the disease-causing mutation, which might be decisive for full expression of the disease phenotype. The application of vascular cells for autologous cell replacement therapy or vascular engineering derived from immune-compatible iPSCs possesses huge clinical potential, but the large-scale production of vascular-specific lineages for regenerative cell therapies depends on well-defined, highly reproducible culture and differentiation conditions. This review will focus on the different strategies to derive vascular cells from human iPSCs and their applications in regenerative therapy, disease modeling and drug discovery approaches.     

Cystatin C inhibits amyloid-beta deposition in Alzheimer's disease mouse models

Using transgenic mice expressing human cystatin C (encoded by CST3), we show that cystatin C binds soluble amyloid-beta peptide and inhibits cerebral amyloid deposition in amyloid-beta precursor protein (APP) transgenic mice. Cystatin C expression twice that of the endogenous mouse cystatin C was sufficient to substantially diminish amyloid-beta deposition. Thus, cystatin C has a protective role in Alzheimer's disease pathogenesis, and modulation of cystatin C concentrations may have therapeutic implications for the disease.     

Cortisone sensitive T-cells in Peyers' patches.

Pretreatment of donor lymphoid cells with cortisone has been shown to depress the T-cell subpopulation responsible for cellular proliferation in the GVH reaction. A quantitative assay as well as the histological criteria of the GVH reaction have been used in this study to demonstrate the presence of cortisone-sensitive T-cells within the Peyer's patches as well as in the spleen and mesenteric lymph nodes in the rat.     

Tracking prions: the neurografting approach

The physical nature of the agent that causes transmissible spongiform encephalopathies (the 'prion'), is the subject of passionate controversy. Investigation of it has benefited tremendously from the use of transgenic and knockout technologies. However, prion diseases present several other enigmas, including the mechanism of brain damage and how the affinity of the agent for the central nervous system is controlled. Here we show that such questions can be effectively addressed in transgenic and knockout systems, and that pathogenesis may be clarified even before we can be certain about the nature of the infectious agent. Availability of mice overexpressing the Prnp gene (which encodes the normal prion protein) and Prnp knockout mice allows for selective reconstitution experiments aimed at expressing PrP in specific portions of the brain or in selected populations of hemato- and lymphopoietic origin. We summarize how such studies can offer insights into how prions administered to peripheral sites can gain access to central nervous tissue, and into the molecular requirements for spongiform brain damage.     

Forecasting the Antwerp maritime steel traffic flow: A case study

This paper uses multivariate time series models to specify the maritime steel traffic flow in the port of Antwerp. The time series considered are the total outgoing and total incoming maritime steel traffic and the total steel production in the EEC. The obtained time series models provide useful insight into the general behaviour of the maritime steel traffic flow during the period 1971–82. In particular, they provide a quantitative interpretation of important changes which took place in the European steel industry during that period. The multivariate time series models produce forecasts which are a substantial improvement over those obtained by univariate time series models. This is especially the case for the series of total incoming maritime steel traffic in the port of Antwerp, when differencing and transformation of the original data are applied.     

Beitrag zur Ätiologie der Hexenbesenkrankheit der KakteeOpuntia tuna (=tuna monstrosa)

Summary Mycoplasma-like bodies, as well as virus-like particles, were observed in phloem elements ofOpuntia tuna monstrosa. The mycoplasma-like bodies, but not the virus-like particles, disappeared in tetracycline hydrochloride treated plants, which indicated a mycoplasma etiology of the witches' broom disease ofOpuntia tuna.

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This investigation was supported, in part, by a grant from the National Science Foundation No. GB-11861, Washington, D.C.     

Endocytosis and inositol hexakisphosphate levels inras transformants ofDictyostelium discoideum amoebae

Summary Fluid-phase pinocytosis kinetics and lysosomal enzyme secretion parameters were measured inDictyostelium discoideum amoebae constructed from strain AX3 by transformation with a multicopy plasmid carrying either a normalras gene (ras-Gly12), a mutatedras gene (ras-Thr12) or by the vector carrying the geneticin resistance gene only (pDNEO2). It was found that the pinocytosis rate and extent as well as the lysosomal enzyme secretion were slightly different in the three strains. These changes, however, were related to minor modifications of the cellular volumes. The overall concentration of inositol hexakisphosphate was similar in the three strains.This work was supported in part by a grant from the Ligue Nationale Française contre le Cancer (n^o 880258) to MS, and by a grant from the Fonds National Suisse de la Recherche Scientifique (No. 3.623-087) to CR.     

Elevated c-myc expression facilitates the replication of SV40 DNA in human lymphoma cells

The v-myc oncogene can induce tumours in haematopoietic, mesenchymal and epithelial tissues. The corresponding c-myc proto-oncogene can contribute to the genesis and/or the progression of an equally wide variety of tumours when activated by retroviral insertions, chromosomal translocations or gene amplification. The c-myc gene product is a DNA-binding, nuclear phosphoprotein that is involved in the control of cell proliferation and possibly in DNA synthesis. The replication of Simian virus 40 (SV40) is a useful model system to study eukaryotic DNA replication as the virus relies almost entirely on cellular DNA replication apparatus. The SV40-based vector, pSVEpR4, replicates poorly in the human BJAB lymphoma line and in most human cells, but replicates well in Burkitt lymphoma lines, which have fused immunoglobulin and c-myc genes, resulting in high c-myc expression. Cotransfection of the BJAB cells with a c-myc-expressing construct (pI4-P6) increased the replication of pSVEpR4 tenfold. Our findings indicate that overexpression of the c-myc gene product allows the replication of SV40 in human lymphoma cells, suggesting that c-myc is involved in the control of replication.